ICARE Newsletter Winter 2021

Inherited Breast Cancer Genes: Two New Important Articles Just Released

Results of a United States (U.S.)-based study1 and an international study2 were released in January in the New England Journal of Medicine and provide a much clearer picture about the role of inherited breast cancer genes in women without a family history of cancer, and how common these genes may be in the general population. In both the U.S. study (to which ICARE contributed) and the international study, 8 genes — BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 — had a significant association with breast cancer risk. In addition, for MSH6 variants this significant association was only observed in the international study; and for CDH1 variants only in the U.S. study. As outlined in the excellent accompanying editorial written by Dr. Steven Narod,3 the majority of mutations among those with breast cancer were in BRCA1, BRCA2, and PALB2, whereas among those without, the majority were in CHEK2 and ATM (according to Table 1 of the article by Dorling et al.2 and Table 2 of the article by Hu et al.1). This is a big difference because it clearly shows that risks are much higher for BRCA1, BRCA2, and PALB2; whereas with CHEK2 and ATM, the risks are lower, yet these gene mutations are much more common in the general population. Ultimately, these studies help establish genes that do versus do not confer breast cancer risks.

1Hu, et al. N Engl J Med. 2021 Jan. PMID 33471974. 2Dorling, et al. N Engl J Med. 2021 Jan. PMID 33471991. 3Narod. N Engl J Med. 2021 Jan. DOI: 10.1056/NEJMe2035083.




ICARE Newsletter Winter 2021

Updates to National Comprehensive Cancer Network (NCCN) Guidelines Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic

Released September 8th, 2020:

Genetic testing criteria by cancer type:

Breast Cancer:

  • Broadened to include relatives with ALL grades of prostate cancer (not just high-grade)
  • Having multiple breast cancer diagnoses no longer depends on whether the diagnoses were on two different breasts

Prostate Cancer:

  • Now includes cribriform histology and ANY risk group (not just high-grade prostate cancer)
  • Only first-degree relatives should be offered genetic testing

Pancreatic Cancer:

  • Only first-degree relatives should be offered genetic testing

 

Released September 8th, 2020:

Breast cancer risk management recommendations by gene:

  • NBN: high-risk breast screening was removed as there is insufficient evidence to support high breast cancer risks
  • BARD1: added consideration for high-risk breast screening starting at age 40
  • RAD51C & RAD51D: risks for triple-negative breast cancer were broadened to include potential increase in female breast cancer risk
  • BRCA1/2: in men with gynecomastia, added consideration for annual mammogram at age 50 (or 10 years before earliest male breast cancer diagnosis in the family)

 

Released November 20th, 2020:
Inherited cancer gene tables expanded to include more detailed risk information, level of risk, and strength of evidence

Check out the full NCCN guidelines by creating a FREE account at: https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf




ICARE Newsletter Winter 2021

Study Suggests Low Yield of MRI Surveillance After Bilateral Mastectomy

A study of 159 women, including BRCA1/2 carriers, who had a bilateral mastectomy with reconstruction and underwent breast MRI screening, showed few women had detection of breast cancer through MRI after their bilateral mastectomy. These results support the recommendation that BRCA1/2 carriers with or without breast cancer who have a bilateral mastectomy with reconstruction do not need breast MRIs for screening.

Golan, et al. Breast Cancer Res Treat. 2019 Apr. PMID: 30511241.




ICARE Newsletter Winter 2021

Assessing How Pregnancy and Breastfeeding May Affect Cancer Risks in BRCA Carriers

Results of a recently published study suggested that pregnancy after breast cancer in BRCA carriers does not lead to a worse outcome in women or their fetuses.1 This information is reassuring for BRCA carriers who have had a prior diagnosis of breast cancer and are considering having children. In another study among female BRCA carriers which included ICARE participants, breastfeeding reduced the risk of ovarian cancer.2 The risk reduction was highest in those who breastfed for 7 months or longer and completed childbearing by age 35.

1Lambertini, et al. J Clin Oncol. 2020 Sep. PMID: 32673153. 2Kotsopoulos, et al. Gynecol Oncol. 2020 Dec. PMID: 33010967.




ICARE Newsletter Winter 2021

Inherited Cancer Treatment: Updates and Relevant Policies

Over the last several months, the American Society of Clinical Oncology published a number of guidelines related to the use of PARP inhibitors among those with BRCA-associated cancers, including guidelines focused on ovarian cancer,1 metastatic pancreatic cancer,2 and breast cancer.3 Additionally, costs of drugs also have great potential to influence policy, highlighting the importance of studies that suggest cost effectiveness when using PARP inhibitors to treat BRCA-associated pancreatic4 and ovarian cancer.5

1Tew, et al. J Clin Oncol. 2020 Oct. PMID: 32790492. 2Sohal, et al. J Clin Oncol. 2020 Aug. PMID: 32755482. 3Tung, et al. J Clin Oncol. 2020 Jun. PMID: 32243226. 4Wu, et al. J Natl Compr Canc Netw. 2020 Nov. PMID: 33152708. 5Muston, et al. Gynecol Oncol. 2020 Nov. PMID: 32951894.




ICARE Social Media Post January 2021

Sharing Genetic Test Results with Family Members of BRCA, PALB2, CHEK2, and ATM

Check out a new article by the ICARE team, published in Patient Education and Counseling, evaluating the motivators and barriers to sharing personal genetic test results with family members. The article is 𝗳𝗿𝗲𝗲 to access and download 𝘂𝗻𝘁𝗶𝗹 𝗠𝗮𝗿𝗰𝗵 𝟱𝘁𝗵 at: https://www.sciencedirect.com/science/article/pii/S0738399120306832




ICARE Publication January 2021

Sharing genetic test results with family members of BRCA, PALB2, CHEK2, and ATM carriers

Abstract
Objective: This study explored motivators and challenges/barriers to sharing personal genetic test results (GTR) with family members (FM).

Methods: Semi-structured, in-depth interviews were conducted with 62 women who had a pathogenic or likely pathogenic (P/LP) variant in a BRCA, PALB2, CHEK2, or ATM gene. Selective qualitative data analysis focused on eliciting motivators and challenges/barriers identified by participants when sharing their GTR with FM.

Results: Motivators to sharing personal GTR with FM included: health protection and prevention; moral obligation; decisional empowerment; familial ties; written resources; and contextualization for a familial cause for cancer. Challenges/barriers to family sharing included: concern for FM reactions; complexities of information; lack of closeness; perceived relevance; and emotional impact.

Conclusions: All motivators and challenges/barriers were identified across BRCA and non-BRCA carriers, demonstrating commonalities in family sharing of GTR among high- to moderate-penetrance hereditary BC (breast cancer) genes. Despite challenges/barriers, participants disclosed their GTR with most close FM, yet restrictions in communication and/or strain on the timing, manner of disclosing, and strategies used varied across certain FM.

Practice implications: These findings offer healthcare providers and researchers preliminary practical implications for broadly improving family sharing interventions across P/LP variants in BC risk genes by demonstrating important elements to include in family sharing letters.

Dean M, et al. Sharing genetic test results with family members of BRCA, PALB2, CHEK2, and ATM carriers. Patient Educ Couns. 2021 Jan 5; Online ahead of print. PMID: 33455826.

 




ICARE Social Media Post December 2020

Genetic Testing in Women with Breast Cancer

Approximately 4,000 women with breast cancer were tested for mutations in nine breast cancer genes – 6.2% had mutations in at least one of the nine genes, and 2.7% had mutations in either 𝘽𝙍𝘾𝘼1 or 𝘽𝙍𝘾𝘼2. Comparisons between women who did versus did not meet National Comprehensive Cancer Network (NCCN) guidelines for testing showed that:
 
­- Sensitivity of NCCN criteria was:
70% for any of the nine genes
87% for 𝘽𝙍𝘾𝘼1/2
 
– Sensitivity when including all women diagnosed with breast cancer at or before age 65 was:
>90% for any of the nine genes
>98% for 𝘽𝙍𝘾𝘼1/2
­
– Specificity of NCCN criteria was 53%, which dropped to 22% when including all women diagnosed with breast cancer at or before age 65.
 
These expanded criteria required testing 31% more women compared to NCCN criteria, with 21% remaining untested. This study provides us with additional information to direct the refinement of guidelines, given that we need to balance yield of testing with the added resources needed to expand testing criteria.
 
Check out the original article at: https://ascopubs.org/doi/full/10.1200/JCO.19.02190



ICARE Social Media Post December 2020

Cost-Effectiveness of Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer

For further information, read the article available at: https://jnccn.org/…/journals/jnccn/18/11/article-p1528.xml



ICARE Publication December 2020

Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women

Abstract

BackgroundThe risks of breast cancer in African American (AA) women associated with inherited mutations in breast cancer predisposition genes are not well defined. Thus, whether multigene germline hereditary cancer testing panels are applicable to this population is unknown. We assessed associations between mutations in panel-based genes and breast cancer risk in 5054 AA women with breast cancer and 4993 unaffected AA women drawn from 10 epidemiologic studies.

MethodsGermline DNA samples were sequenced for mutations in 23 cancer predisposition genes using a QIAseq multiplex amplicon panel. Prevalence of mutations and odds ratios (ORs) for associations with breast cancer risk were estimated with adjustment for study design, age, and family history of breast cancer.

ResultsPathogenic mutations were identified in 10.3% of women with estrogen receptor (ER)-negative breast cancer, 5.2% of women with ER-positive breast cancer, and 2.3% of unaffected women. Mutations in BRCA1, BRCA2, and PALB2 were associated with high risks of breast cancer (OR = 47.55, 95% confidence interval [CI] = 10.43 to >100; OR = 7.25, 95% CI = 4.07 to 14.12; OR = 8.54, 95% CI = 3.67 to 24.95, respectively). RAD51D mutations were associated with high risk of ER-negative disease (OR = 7.82, 95% CI = 1.61 to 57.42). Moderate risks were observed for CHEK2, ATM, ERCC3, and FANCC mutations with ER-positive cancer, and RECQL mutations with all breast cancer.

ConclusionsThe study identifies genes that predispose to breast cancer in the AA population, demonstrates the validity of current breast cancer testing panels for use in AA women, and provides a basis for increased referral of AA patients for cancer genetic testing.

Palmer J, et al. Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women. J Natl Cancer Inst. 2020 Dec 14;112(12):1213-1221. PMID: 32427313.




ICARE Social Media Post December 2020

Broader Germline Testing for Urothelial Cancer

The most common inherited form of urothelial cancers is Lynch Syndrome. However, a study showed that of 586 individuals with urothelial cancer, 80 had a mutation in an inherited cancer gene (14%). Mutations in several genes were observed; however, 𝙈𝙎𝙃2 and 𝘽𝙍𝘾𝘼2 were both significantly associated with urothelial cancer (odds ratio of 3.7).
 
Confirmatory studies are needed to look at this question further. In the meantime, it may be particularly important to consider genetic testing for individuals with urothelial cancer, especially those diagnosed at a young age.
 
Check out the original article at: https://www.ncbi.nlm.nih.gov/pubmed/31794323



ICARE Social Media Post November 2020

Olaparib May Be Cost-Effective Maintenance Treatment For Women With Newly Diagnosed Ovarian Cancer and BRCA Mutation

For further information, view the article available at: https://www.gynecologiconcology-online.net/…/fulltext




ICARE Social Media Post November 2020

Impact of Pregnancy After Breast Cancer in Women With Deleterious Germline BRCA Mutations

Check out the original article by visiting: https://pubmed.ncbi.nlm.nih.gov/32673153/




ICARE Social Media Post November 2020

ASCO Guideline Updates: Breast Cancer

The American Society of Clinical Oncology (ASCO) published updated guidelines for the management of hereditary breast cancer for the following gene carriers:
 
𝘽𝙍𝘾𝘼1/2
• Consider breast-conserving therapy
• Consider nipple-sparing mastectomy, if medically appropriate
• Advanced breast cancer:
⫸ PARP inhibitors (olaparib, talazoparib) preferred over non-platinum single agent chemotherapy
⫸ Platinum agents are recommended versus taxanes
𝙏𝙋53
• Mastectomy is advised
• Radiation therapy is contraindicated except for those at risk for locoregional recurrence
 
For more information, check out the full article at: https://ascopubs.org/doi/full/10.1200/JCO.20.00299



ICARE Social Media Post November 2020

B-GREAT 2020 Newsletter

The B-GREAT 2020 Newsletter is now available! Check out this latest edition for research updates and information about racial inequalities in healthcare. You can read the newsletter by visiting: https://bgreatinitiative.inheritedcancer.net/wp-content/uploads/BGREAT-Newsletter-2020.pdf. Please feel free to share with family members, friends, and/or your healthcare providers. 

We will be publishing these newsletters twice a year starting in 2021. Stay tuned for our March and October 2021 editions!




ICARE Publication November 2020

Family communication of genetic test results among women with inherited breast cancer genes

Abstract

Identification of inherited breast cancer may guide care. These benefits can be amplified through communication of genetic test results with at-risk family members and subsequent family testing (FT). Females with a pathogenic/likely pathogenic (P/LP) variant in BRCA1/2, PALB2, CHEK2, and/or ATM were surveyed about family communication (FC) of genetic test results and FT. Comparisons were made across genes. The 235 participants with P/LP variants (186 BRCA1/2, 28 PALB2, 15 CHEK2, and 6 ATM) had a median age of 54 and most were non-Hispanic whites (89%) with a prior breast cancer diagnosis (61%). When controlling for other variables, FC was higher among younger participants (p<.0001), those with high FC self-efficacy (p=.019), and those with P/LP variants in BRCA1/2 compared to PALB2 (p =.040) and ATM/CHEK2 (p =.032). Higher rates of FC and FT were also observed among female relatives and relatives of closer kinship. Overall 94% of participants would find one or more resources helpful with FC and 70% reported using FC resources when telling family members about their genetic test result. The three most commonly used resources included the following: (a) a family sharing letter (38%); (b) printed materials (30%); and (c) web-based information (23%). Among the 86% who spoke with a genetic counselor (GC), 93% were given at least one FC resource and the three most common resources GCs provided to participants overlapped with the resources participants would find helpful and those that were used. Our results suggest lower FC and FT rates among women with P/LP variants in genes other than BRCA1/2, the reasons for which should be evaluated in future studies. As more data to refine cancer risks and management are generated across these other inherited breast cancer genes, strategies to improve FC and FT are needed to amplify the benefits of genetic testing.

Cragun D, et al. Family communication of genetic test results among women with inherited breast cancer genes. J Genet Couns. 2020 Nov 10; Online ahead of print. PMID: 33174380.




ICARE Social Media Post November 2020

Clinical Trial Participation Powers Patient’s Positive Attitude

Brooke Thomas has leaned on 12 years of experience as a medical social worker and found ways to stay positive and upbeat through it all – and she has a lot to be positive about these days, thanks to an amazing response to her treatment as part of a clinical trial at Vanderbilt-Ingram Cancer Center. The trial involves PARP inhibitors, a class of drugs with an expanding role in cancer treatment.

http://spr.ly/6186G7Ir8




ICARE Social Media Post October 2020

Polygenic Risk Scores in Refining Breast Cancer Risks

For further information, view the article available at: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767768




ICARE Social Media Post October 2020

New ASCO Guidelines On Use Of PARP Inhibitors To Manage Ovarian Cancer

New guidelines for the use of PARP inhibitors to treat ovarian cancer among those with BRCA1 or BRCA2 mutations were published through the American Society of Clinical Oncology (ASCO) to guide providers about the role of this class of drugs in the management of this type of cancer.

Link to the guidelines are available at: https://ascopubs.org/doi/full/10.1200/JCO.20.01924




ICARE Featured Video September & October 2020

NCCN Genetic/Familial Breast, Ovarian, and Pancreatic Guidelines

Below you may watch a featured video from the September 2020 and October 2020 Genetics Case Conference, which outlined updates to the National Comprehensive Cancer Network (NCCN) guidelines.

Check out the full guidelines by creating a FREE account at: https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf




ICARE Social Media Post October 2020

Addition of Veliparib to Carboplatin/Paclitaxel in Previously Treated Patients With BRCA-Mutated Advanced Breast Cancer

Among BRCA carriers with metastatic breast cancer, the combination of veliparib AND chemotherapy with platinum-based agents (carboplatin) and taxanes (paclitaxel) led to a longer duration of progression free survival (disease that did not progress), compared to those treated with ONLY chemotherapy.

To read the full article visit: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30447-2/fulltext
[This finding was previously outlined last year based on the ESMO 2019’s BROCADE3 abstract; however, the full article was not published until recently]




ICARE Publication September 2020

Breastfeeding and the risk of epithelial ovarian cancer among women with a BRCA1 or BRCA2 mutation

Abstract
Objective: BRCA mutation carriers face a high lifetime risk of developing ovarian cancer. The strong inverse association between breastfeeding and the risk of ovarian cancer is established in the general population but is less well studied among women with a germline BRCA1 or BRCA2 mutation.

Method: Thus, we conducted a matched case-control analysis to evaluate the association between breastfeeding history and the risk of developing ovarian cancer. After matching for year of birth, country of residence, BRCA gene and personal history of breast cancer, a total of 1650 cases and 2702 controls were included in the analysis. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) associated with various breastfeeding exposures.

Results: A history of ever-breastfeeding was associated with a 23% reduction in risk (OR = 0.77; 95%CI 0.66-0.90; P = 0.001). The protective effect increased with breastfeeding from one month to seven months after which the association was relatively stable. Compared to women who never breastfed, breastfeeding for seven or more months was associated with a 32% reduction in risk (OR = 0.68; 95%CI 0.57-0.81; P < 0.0001) and did not vary by BRCA gene or age at diagnosis. The combination of breastfeeding and oral contraceptive use was strongly protective (0.47; 95%CI 0.37-0.58; P < 0.0001).

Conclusions: These findings support a protective effect of breastfeeding for at least seven months among women with a BRCA1 or BRCA2 mutation, that is independent of oral contraceptive use.

Kotsopoulos J, et al. Breastfeeding and the risk of epithelial ovarian cancer among women with a BRCA1 or BRCA2 mutation. Gynecol Oncol. 2020 Dec; 159(3):820-826. Epub 2020 Sep 30. PMID: 33010967.




ICARE Social Media Post September 2020

Rucaparib May Have Antitumor Activity in Male BRCA Carriers with Metastatic Prostate Cancer

For further information, view the article available at: https://ascopubs.org/doi/full/10.1200/JCO.20.01035




ICARE Publication September 2020

Strategies to enhance identification of hereditary breast cancer gene carriers

No abstract available

Reid S, et al. Strategies to enhance identification of hereditary breast cancer gene carriers. Expert Rev Mol Diagn. 2020 Sep; 20(9):861-865. Epub 2020 Sep 11. PMID: 32856489. 




ICARE Social Media Post September 2020

NCCN Breast Cancer Risk Management Updates by Gene

The National Comprehensive Cancer Network (NCCN) released new guidelines on September 8th, 2020, which included updates to breast cancer risk management recommendations by gene as follows: 
  • NBN – high-risk breast screening was removed as there is insufficient evidence to support high cancer risks
  • BARD1 – added consideration for high-risk breast screening starting at age 40 
  • RAD51C & RAD51D – risks for triple negative breast cancer were broadened to include potential increase in female breast cancer risk
  • BRCA1/2 – in men with gynecomastia, added consideration for annual mammogram at age 50 (or 10 years before earliest male breast cancer diagnosis in the family) 
You can check out the full guidelines by creating a FREE account at: https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf 



ICARE Social Media Post August 2020

Older Women with Breast Cancer Have Higher Risks of Ovarian and Other Cancers

Among 4,500 post-menopausal women with breast cancer, 3.55% had a mutation in a gene associated with inherited breast cancer (3-fold higher than what was seen among women who were cancer-free).

BRCA1/2 mutations were seen more frequently in women diagnosed with breast cancer at or below age 65 (2.21%) compared to those diagnosed after age 65 (1.09%).

This study provides additional information to take into consideration when refining national practice guidelines for genetic testing for inherited cancer.

Check out the original article at: https://jamanetwork.com/journals/jama/article-abstract/2762602?resultClick=1




ICARE Social Media Post August 2020

MRI Surveillance Has Very Low Yield After Bilateral Mastectomy and Reconstruction

A study of 159 women, including BRCA carriers, who had bilateral mastectomy with reconstruction, underwent breast MRI screening. The results showed few women had detection of breast cancer through MRI, after their bilateral mastectomy. These results support the recommendation against screening MRI in women who have had bilateral mastectomy with reconstruction due to a diagnosis of cancer or to reduce their risk of developing breast cancer.

Check out the full article at https://www.ncbi.nlm.nih.gov/pubmed/30511241




ICARE Newsletter Summer 2020

Identifying Individuals At-Risk for Inherited Cancer

We have known for a while that many people who have mutations in BRCA1/2 and other inherited cancer risk genes are unaware of their mutation as they have not yet had genetic testing. A recent study among women aged 20 or older living in California and Georgia, which included almost 80,000 breast cancer patients and 6,000 ovarian cancer patients, found that about a quarter of those with breast cancer and a third of those with ovarian cancer had genetic testing [1]. Of individuals who had testing, 7.8% of those with breast cancer and 14.5% with ovarian cancer were found to have a mutation in an inherited cancer gene [1]. Testing among breast cancer patients was lower as age and poverty level increased, but was similar across racial/ethnic groups (such as Whites, Blacks, American Indians, Asians, and Hispanics) [1]. In contrast, for ovarian cancer patients, testing was lower among Black compared to White patients (21.6% versus 33.8%) and among those without insurance compared to those with insurance (20.8% versus 35.3%) [1]. These results continue to identify substantial gaps in testing among cancer patients, and highlight existing disparities in cancer care which need to be addressed and improved.

Findings from another study based in a health system where patients were insured and had access to genetic services were recently published [2]. Results showed that annual rates of genetic testing increased between 2005 to 2015 among women with breast and ovarian cancer overall; however, rates of genetic testing among women with newly diagnosed breast and ovarian cancers fell from 71.5/1000 person years in 2005 to 44.4/1000 person years in 2015 [2]. This study highlights that many women who are eligible to have BRCA1/2 testing covered by their health insurance did not have it, suggesting there is much work to be done for more people to benefit from testing and the medical care options that testing may provide.

[1] Kurian, et al. J Clin Oncol. 2019 May. PMID 30964716; [2] Knerr, et al. J Natl Cancer Inst. 2019 Feb. PMID 30753636.




ICARE Newsletter Summer 2020

Treatment Advances Among BRCA1/2 Carriers

There continue to be ongoing advances in treatment studies among those with inherited cancer gene mutations, which are rapidly being followed by FDA approval for specific cancer treatments. Select studies and advances are summarized below:

BRCA1/2 Carriers: 

Breast Cancer: For those with later stage or metastatic breast cancer, the FDA currently has approvals for the use of PARP inhibitors, yet the impact of combination therapy is still under investigation. A recent study suggested veliparib (a PARP inhibitor) in combination with chemotherapy showed benefit [1]. For those with early stage breast cancer, a recent study suggested benefit from talazoparib (another PARP inhibitor) [2]. New research suggests that platinum-based agents, which have been suggested to be of particular benefit to treat BRCA1/2-related breast cancer, are less effective than previously thought in the neoadjuvant setting (treatment given before surgery) [3], and among those with early stage triple negative breast cancer in the neoadjuvant setting [4].

Ovarian Cancer: For those with advanced ovarian cancer, the FDA recently approved niraparib (a PARP inhibitor) as first-line maintenance treatment. Among those with platinum-sensitive relapsed ovarian cancer who had received at least two prior lines of platinum-based chemotherapy, olaparib (another PARP inhibitor) showed potential benefit [5]. Subsequently, the FDA approved olaparib as first-line maintenance treatment in those with complete or partial response to first-line platinum-based chemotherapy.

Prostate Cancer: Among those with metastatic castration-resistant prostate cancer, a recent study suggested that rucaparib (a PARP inhibitor) may have antitumor activity [6], which then provided data to support FDA approval of rucaparib among those treated with anti-androgens and/or other treatments. Olaparib (another PARP inhibitor) also received FDA approval recently for a similar indication.

Pancreatic Cancer: Among BRCA1/2 or PALB2 carriers with stage 3 or 4 pancreatic cancer, the addition of veliparib (a PARP inhibitor) did not provide additional benefit over cisplatin and gemcitabine alone [7].

[1] Dieras, et al. ESMO 2019 Congress. 2019 Sep. Available at: https://tinyurl.com/dieras2019; [2] Litton, et al. J Clin Oncol. 2020 Feb. PMID: 31461380; [3] Tung, et al. J Clin Oncol. 2020 May. PMID: 32097092; [4] Pohl-Rescigno, et al. JAMA Oncol. 2020 Mar. PMID: 32163106; [5] Penson, et al. J Clin Oncol. 2020 Feb. PMID: 32073956; [6] Abida, et al. J Clin Oncol. 2020 Aug. PMID: 32795228; [7] O’Reilly, et al. J Clin Oncol. 2020 May. PMID: 31976786; 




ICARE Newsletter Summer 2020

Guideline-Concordant Care Among Women with Inherited Cancer Gene Mutations

Testing for inherited cancer among breast cancer patients has tremendous potential to guide appropriate care following testing. Yet, a number of efforts suggest that women are not consistently receiving care according to current national guidelines based on their genetic test result. In fact, results from studies suggest many women for whom risk-reducing mastectomy would not be recommended based solely on their genetic test result, may be receiving this procedure. Specifically, high rates of bilateral mastectomy have been reported among those with a BRCA1/2 variant of uncertain significance [1] as well as those with non-BRCA1/2 moderate penetrance genes [2,3], suggesting potential overtreatment. Additionally, a recently published cancer registry-based study suggested that those with a BRCA1/2 mutation may be more likely to receive bilateral mastectomy for a unilateral tumor, less likely to receive post-lumpectomy radiotherapy, and more likely to receive chemotherapy for early-stage, ER/PR-positive disease [2]. Similarly, we have previously reported on risk-reducing oophorectomies conducted among BRCA1/2 carriers, which showed lower rates among Black women compared to non-Hispanic Whites [4]. More recently, our study based directly on ICARE participants, as well as another registry study, suggested there may be potential overtreatment with oophorectomy among women with non-BRCA1/2 inherited breast cancer genes in which oophorectomy is not generally recommended for risk reduction based on current ovarian cancer risk estimates [3,5]. These findings highlight the importance of promoting guideline-adherent care and avoiding overtreatment.6

[1] Kurian, et al. J Clin Oncol. 2017 Apr. PMID: 28402748; [2] Kurian, et al. JAMA Oncol. 2020 Feb. PMID: 32027353; [3] Cragun, et al. Breast Cancer Res Treat. 2020 Jul. PMID: 32445176; [4] Cragun, et al. Cancer. 2017 Jul. PMID: 28182268; [5] Domchek, et al. J Clin Oncol. 2020 May. Available at: https://tinyurl.com/domchek2020; [6] MyGeneCounsel. 2019 Oct. Available at: https://tinyurl.com/MyGeneCounselWhitePaper




ICARE Social Media Post August 2020

Presymptomatic BRCA1/2 Carriers May Have Better Outcomes

Check out the article at: https://jamanetwork.com/journals/jamaoncology/article-abstract/2768011




ICARE Social Media Post July 2020

Cancer Risks in Men with BRCA1 and BRCA2 Pathogenic Variants

Check out the article at: https://jamanetwork.com/journals/jamaoncology/article-abstract/2767423




ICARE Social Media Post July 2020

BRCA1/2 and Other Gene Carriers with Breast Cancer Don’t Always Receive Recommended Treatment

BRCA1/2 and other gene mutation carriers with early stage breast cancer are not always receiving cancer treatment as recommended by national guidelines.

Even though more and more people have been tested for hereditary cancer over the years, using this information accurately to guide treatment has not been as successful.

These findings highlight the need for using this information better to help guide appropriate breast cancer treatment, including radiation treatment and chemotherapy.

Check out the full article at https://jamanetwork.com/journals/jamaoncology/fullarticle/2760433.




ICARE Social Media Post June 2020

Advances in Treatment for BRCA-Mutated Triple Negative Breast Cancer

In a study of 914 women with different breast cancer subtypes, overall pathologic complete response rates were:

  • Higher in those with BRCA1/2 mutations (60.4% versus 46.7%)
  • No differences were seen in those with mutations in other inherited cancer genes
  • Among patients with triple-negative breast cancer, BRCA1/2 mutations had highest response rates to treatment in both study arms (Arm 1: 74.3%, Arm 2: 64.7%) compared to non-carriers (Arm 1: 47%; Arm 2: 45%)
  • Among those without triple negative disease, BRCA1/2 carriers had higher response rates compared to non-carriers (31.8% vs 11.9%)
  • Both platinum-based and non-platinum-based treatment may be of benefit to BRCA1/2 carriers with triple negative breast cancer in the neoadjuvant setting, but additional studies are needed to further evaluate these findings

Check out the original article at: https://jamanetwork.com/journals/jamaoncology/article-abstract/2762579




ICARE Social Media Post June 2020

Community Spotlight: Patricia Blumenthal

In every ICARE Newsletter we feature an ICARE participant as a community spotlight. Our community spotlight in our Summer 2018 ICARE Newsletter is Patricia Blumenthal, who was found to have a BRCA2 mutation.

Check out her story at: https://inheritedcancer.net/community-spotlight/




ICARE Social Media Post June 2020

Advances in BRCA1/2 Breast Cancer Treatment

Through a randomized phase 2 study (called the INFORM trial) among BRCA1/2 carriers with breast cancer, cisplatin was no better in inducing pathologic complete remission compared to AC. The pathologic complete remission rate was 18% for cisplatin and 26% for AC. Cisplatin is not better than other chemotherapy for induction therapy for breast cancers in BRCA1/2 mutation carriers.

This study corrects data from prior studies, some of which were observational studies prone to bias. Specifically, results from this trial provides new information which suggests less efficacy of platinum-based therapies than previously thought. This information should be considered when choosing the best treatment for these women.

Check out original article at https://ascopubs.org/doi/pdf/10.1200/JCO.19.03292.

Check out ASCO’s commentary at: https://www.ascopost.com/issues/february-25-2020/neoadjuvant-cisplatin-for-brca-mutation-carriers-pruning-the-dead-branches/




ICARE Social Media Post June 2020

Advances in Treatment for Pancreatic Cancer: Cisplatin + Gemcitabine

In BRCA1/2 or PALB2 carriers with stage 3 or 4 pancreatic cancer, the combination of cisplatin + gemtricitabine with veliparib (a PARP inhibitor), did NOT seem to provide additional benefit over cisplatin + gemtricitabine alone.

Through this phase 2 randomized control trial, response rates in both treatment arms were high with similar overall survival rates. The take-home point is that the cisplatin/gemcitabine regimen showed a tremendous response for these patients (and veliparib did not really provide additional benefit). Additional trials are ongoing to study these drugs further in pancreatic cancer patients.

Check out the full article at https://www.ncbi.nlm.nih.gov/pubmed/31976786




ICARE Social Media Post May 2020

Platinum Based Chemotherapy for Metastatic Pancreatic Cancer

A recent study found that patients with metastatic pancreatic cancer who had mutations in the DNA repair genes (either inherited or just in the tumor) had better clinical outcomes after platinum-based chemotherapy compared to patients without these mutations.

Check out the link to full article: https://clincancerres.aacrjournals.org/content/early/2020/05/20/1078-0432.CCR-20-0418




ICARE Social Media Post May 2020

Cancer Risk Management Among Female BRCA1/2, PALB2, CHEK2, and ATM Carriers in ICARE

A new article was recently published based on data from BRCA1/2, PALB2, CHEK2, and ATM carriers in ICARE. Findings suggest potential overtreatment through risk-reducing surgery among women with pathogenic/likely pathogenic variants in breast cancer genes. This highlights the importance of promoting guideline-adherent, risk-appropriate care.

Check out the full article at https://rdcu.be/b4mbg




ICARE Social Media Post May 2020

Advances in Treatment for Metastatic Prostate Cancer: Olaparib

On May 19, 2020 the FDA approved the use of olaparib (Lynparza) as treatment in BRCA and other gene carriers (homologous recombination repair genes) with metastatic castration-resistant prostate cancer who have been treated with enzalutamide or abiraterone.

Link to full article: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-hrr-gene-mutated-metastatic-castration-resistant-prostate-cancer




ICARE Publication May 2020

Cancer risk management among female BRCA1/2, PALB2, CHEK2, and ATM carriers

Abstract

PurposeIdentification of inherited breast cancer may guide cancer risk management. We sought to compare risk management practices across women with inherited breast cancer genes.

MethodsFemales with a pathogenic/likely pathogenic (P/LP) variant in BRCA1/2, PALB2, CHEK2, and/or ATM were surveyed about cancer risk management. Comparisons were made across genes.

ResultsThe 235 participants with P/LP variants (186 BRCA1/2, 28 PALB2, 15 CHEK2, and 6 ATM) had a median age of 54 and 61% had a prior breast cancer diagnosis. For women with P/LP variants in BRCA1/2, PALB2, and ATM/CHEK2, bilateral mastectomy (BM) rates were 79%, 61%, and 52%, and bilateral oophorectomy (BO) rates were 89%, 30%, and 37%, respectively. Among women with P/LP variants in PALB2 and ATM/CHEK2, 27% of those who had a BO had a family history of ovarian cancer. Contralateral mastectomy rates for women with P/LP variants in PALB2 and ATM/CHEK2 with unilateral breast cancer were 60% and 58%, and BM rates for those without breast cancer were 57% and 29%, respectively.

ConclusionThese findings suggest high rates of both contralateral mastectomies among those with unilateral breast cancer and BM among those without a breast cancer diagnosis across women with P/LP variants in high and moderate penetrance breast cancer genes. BO was also often utilized for risk reduction across these women. These findings suggest potential overtreatment through risk-reducing surgery, and highlight the importance of promoting guideline-adherent, risk-appropriate care.

Cragun D, et al. Cancer risk management among female BRCA1/2, PALB2, CHEK2, and ATM carriers. Breast Cancer Res Treat. 2020 Ju;182(2):421-428. Epub 2020 May 22. PMID: 32445176.




ICARE Social Media Post May 2020

Advances in Treatment for Metastatic Prostate Cancer: Rucaparib

On May 15, 2020 the FDA approved the use of rucaparib (Rubraca) as treatment in BRCA carriers with metastatic castration-resistant prostate cancer who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.

Link to full article: https://www.fda.gov/drugs/fda-grants-accelerated-approval-rucaparib-brca-mutated-metastatic-castration-resistant-prostate




ICARE Social Media Post May 2020

Advances in Ovarian Cancer Treatment for BRCA1/2 Carriers: Olaparib & bevacizumab

On May 8, 2020 the FDA approved the use of olaparib (Lynparza) as first-line maintenance treatment in BRCA1/2 carriers (deleterious or suspected deleterious mutations) and/or a genomic instability, with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.

Link to full article: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-plus-bevacizumab-maintenance-treatment-ovarian-fallopian-tube-or-primary




ICARE Social Media Post May 2020

Advances in Ovarian Cancer Treatment for BRCA1/2 Carriers: Olaparib

In recognition of World Ovarian Cancer Day, we’d like to share some exciting results from a study of women with ovarian cancer and a BRCA mutation:

In a recent phase III trial, olaparib (PARP inhibitor) showed improved response and progression-free survival compared with chemotherapy (without platinum) in BRCA carriers with platinum-sensitive relapsed ovarian cancer who had received at least two prior lines of platinum-based chemotherapy.

Among patients treated with olaparib, the objective response rate was 72.2% compared to only 51.4% for patients treated with chemotherapy only. Additionally, the median progression-free survival was 13.4 months for the olaparib group compared to 9.2 months for the chemotherapy group.

Link to full article: https://ascopubs.org/doi/full/10.1200/JCO.19.02745




ICARE Social Media Post May 2020

Advances in Treatment for Metastatic Prostate Cancer: Olaparib

Findings from a recent study showed that olaparib (PARP inhibitor) significantly improved progression-free survival in patients with BRCA1, BRCA2, or ATM genetic alterations. Benefits were also more broadly seen among patients with homologous recombination repair gene defects.

Link to full article: https://www.nejm.org/doi/full/10.1056/NEJMoa1911440
Check out the ASCO post article at: https://www.ascopost.com/news/may-2020/olaparib-for-patients-with-mcrpc-and-homologous-recombination-repair-gene-alterations/




ICARE Social Media Post April 2020

Advances in Treatment for Ovarian Cancer in BRCA1/2 Carriers: Niraparib

On April 29, 2020 the FDA approved the use of niraparib (Zeluja) as first-line maintenance treatment in BRCA1/2 carriers with advanced ovarian cancer!

More details available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-niraparib-first-line-maintenance-advanced-ovarian-cancer




ICARE Social Media Post April 2020

BRCA2: Cancer Risks and Risk Management

Gene: BRCA2

Cancer Risks and Management (per NCCN version 3.2019):

Women:

Breast cancer risk: Elevated at 60%-70% – Recommend clinical breast exam every 6-12 months starting at age 25, annual breast MRI with contrast starting at age 25, and annual mammogram with consideration of tomosynthesis starting at age 30; consider risk-reducing mastectomy.

Ovarian cancer risk: Up to 27% – Recommend risk-reducing bilateral salpingo-oophorectomy (removal of ovaries and fallopian tubes) between ages 40 and 45.

Men and Women:

Pancreatic cancer risk: Elevated – Consider MRI/MRCP or endoscopic ultrasound for BRCA2 carriers with a family history of pancreatic cancer in first-degree relative.

Men:

Breast cancer risk: Breast cancer risk: Elevated at 6%-8% – Recommend annual clinical breast exams starting at age 35.

Prostate cancer risk: Up to 20% – Recommend PSA screening and digital rectal exam starting at age 40.

Inheritance: Autosomal dominant, thus parents, full siblings, and children have a 50% risk for the gene mutation. If both parents have a BRCA2 mutation, the child is at risk for autosomal recessive Fanconi anemia.

Family Testing: At-risk family members should consider genetic counseling and genetic testing. For adult-onset conditions, recommend waiting to perform genetic testing on minors are at least 18 years old.

Reproductive Considerations: Option for preimplantation genetic diagnosis (PGD) may be available to ensure future generations do not inherit the known gene mutation. PGD is a procedure available for certain gene mutations to screen the embryo prior to achievement of pregnancy.

Check out the full management guidelines by creating a FREE account at https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf




ICARE Social Media Post April 2020

ASCO Guideline: Genetic Testing for Ovarian Cancer

The American Society of Clinical Oncology (ASCO) recently published a guideline reinforcing the longstanding recommendation that all women diagnosed with epithelial ovarian cancer (EOC) be offered genetic testing for hereditary ovarian cancer genes.

Many of these women (>15%) have an inherited mutation, most commonly BRCA1 or BRCA2. Identifying BRCA1/2 mutations may help guide cancer treatment.

Check out the full article at: https://ascopubs.org/doi/full/10.1200/JCO.19.02960?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Check out a commentary about the original article at https://www.cancertherapyadvisor.com/home/cancer-topics/gynecologic-cancer/ovarian-cancer-asco-guideline-germline-testing-recommendation-all-women/

Check out NCCN guidelines, which have recommended genetic testing for all ovarian cancer patients https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf




ICARE Newsletter Winter 2020

Treatment Advances Among Those with Inherited Prostate Cancer Predisposition

A recent study reported a high complete response rate among men with a BRCA1/2 mutation with metastatic, castration-resistant prostate cancer who were treated with niraparib (a PARP inhibitor) of 63% compared to 17% in the non-BRCA1/2 group.1 Based on this data, the Federal Drug Administration (FDA) granted breakthrough therapy designation to niraparib on October 3, 2019 to expand the treatment options for men with BRCA1/2 positive, metastatic, castration-resistant prostate cancer.2

1Smith, et al. Presented at 2019 ESMO Congress. 2019 Sept-Oct. Barcelona, Spain. Abstract LBA50. 2Augenstein S. FDA Grants Breakthrough Therapy Designation to Niraparib for mCRPC. 2019 Oct. Available at: https://tinyurl.com/BRCAassociatedprostatecancer.

Social media post: https://tinyurl.com/ICARE20191220




ICARE Newsletter Winter 2020

Treatment Advances Among Those with Inherited Pancreatic Cancer Predisposition

Results from a recent study showed olaparib (a PARP inhibitor) nearly doubled the progression-free survival in BRCA1/2 carriers with metastatic pancreatic cancer.1 Based on this data, the FDA approved the use of olaparib as a first-line maintenance treatment in BRCA1/2 carriers with metastatic, platinum-sensitive pancreatic cancer. This represents another treatment advance in pancreatic cancer and highlights the importance of genetic testing for all patients with pancreatic cancer.

Another recent study among pancreatic cancer patients with a BRCA1/2 or PALB2 mutation showed that response rates after first line treatment with cisplatin/gemcitabine alone was 65.2%, and with addition of veliparib (a PARP inhibitor), it was 74.1%.2 The study evaluated each arm separately and did not compare them. Survival at 2 years and 3 years was also encouraging at 31% and 18%, respectively. These data highlight the importance of conducting testing for inherited cancer among all patients with pancreatic cancer, as this information may guide treatment among those identified to have inherited cancer gene mutations such as BRCA1/2 or PALB2.

1Golan, et al. N Engl J Med. 2019 Jul. PMID: 31157963; 2Helwick, C. The ASCO Post. 2020 Jan. Available at: https://www.ascopost.com/  

Social media post: https://tinyurl.com/ICARE202013  




ICARE Newsletter Winter 2020

Updates to National Comprehensive Cancer Network (NCCN) Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic

There were significant updates and restructuring of the guidelines, with some highlights included below:

  • Substantial reorganization of the guidelines as follows:
    • Now organized by organ site, rather than primarily by certain high penetrance genes
    • Focused efforts to simplify genetic testing criteria
    • Only one flow diagram included, to outline the ‘genetic testing process’
  • Following scenarios now outlined:
    • Situations in which genetic testing may have low yield
    • Situations where referral to a genetics expert is recommended
  • PALB2: Recognized as a high penetrance gene, for which discussion of risk-reducing mastectomy is appropriate
  • BRCA1/2: Prostate cancer screening to be initiated at age 40
  • Pancreatic screening guidance included:
    • STK11 starting at age 30-35
    • CDKN2A starting at age 40
    • BRCA1/2, ATM, MLH1, MSH2, MSH6, EPCAM, PALB2, or TP53: Only if there is a close family member with pancreatic cancer

For the complete updated versions of the NCCN guidelines, please visit NCCN.org

Follow this link to view our social media post: https://tinyurl.com/ICARE2019124

Full press release available at: https://www.nccn.org/about/news/newsinfo.aspx?NewsID=1790




ICARE Newsletter Winter 2020

Updated Pancreatic Cancer Screening Guidelines through CAPS Consortium

The International Cancer of the Pancreas Screening (CAPS) Consortium recently published updated recommendations about pancreatic cancer screening through MRI/magnetic retrograde cholangiopancreatography (MRCP) and/or an endoscopic ultrasound (EUS).1 Specifically, these guidelines now recommend that individuals with a CDKN2A or STK11 mutation begin screening at age 40. Screening for individuals with a BRCA1/2, ATM, PALB2, MLH1, or MSH2 mutation is only recommended if they have at least one first-degree relative with pancreatic cancer, beginning at age 45-50 or 10 years younger than the youngest relative diagnosed with pancreatic cancer. These guidelines were developed through expert consensus based on existing research; however, there remains a need for more information to understand the benefits and risks of pancreatic cancer screening. Both patients and their treating providers should be aware that these guidelines have some differences from the recently published NCCN genetic/familial breast, ovarian, and pancreatic guidelines, as outlined in the table below.2

Age to Begin Pancreatic Cancer Screening per NCCN & CAPS
Gene NCCN (V.1.2020) CAPS (2019)
STK11 Begin at 30-35 Begin at 40
CDKN2A Begin at 40 Begin at 40
BRCA1/2, PALB2, ATM, MLH1, MSH2, MSH6 Begin at 50 Begin at 45-50
EPCAM, TP53 Begin at 50 Not included

1Goggins, et al. Gut. 2020 Jan. PMID: 31672839; 2NCCN Practice Guidelines. V.1.2020. 2019 Dec. Available at: NCCN.org

Social media post: https://tinyurl.com/ICARE202026  




ICARE Newsletter Winter 2020

Ask the Expert

Through each newsletter, we give our participants an opportunity to have their questions answered by experts. If you have a question you would like addressed, please email the study team at ICARE@InheritedCancer.net for consideration in future newsletters. The following question was addressed by Ben Ho Park, MD, PhD, who is the Donna S. Hall Chair in Breast Cancer, Co-Leader of the Breast Cancer Research Program, Associate Director for Translational Research, and Director of Precision Oncology at Vanderbilt-Ingram Cancer Center. Dr. Park is also a Professor of Medicine and Associate Director for Basic and Translational Research in the Department of Medicine’s Division of Hematology and Oncology.  

Q. How is DNA testing done on someone’s tumor different from testing done on someone’s normal DNA from their blood or saliva sample?

A. When we extract DNA from a biopsy or surgical sample of a tumor, usually it is a mixture of both normal cells and tumor cells. This is because normal cells such as blood vessels and blood cells are found within the tumor itself. However, all tumors arise because of changes in our normal DNA. Sometimes we have inherited DNA changes like BRCA1/2, but all tumors, including BRCA1/2-associated tumors, will have additional DNA changes that are present only in the tumor cells. Usually it takes 3 to 8 DNA changes to make a normal cell cancerous. Therefore, when we analyze these changes using a biopsy or surgical sample, we cannot tell whether the changes are in the tumor cells only, or present in both tumor and normal cells, since it is a mixture of these cells. DNA that has changes in normal cells, like BRCA1/2 mutations, are called “germline”. These are DNA changes that a person was born with and present in almost every cell of their body. These DNA changes can be passed to their children.

The reason it is important to test tumor DNA is because it can help guide treatment based on mutations that are found in the tumor cells. However, we can now identify whether a DNA change is in the germline vs. the tumor only by also testing normal DNA separately, usually through a blood or saliva sample and comparing germline vs. tumor DNA changes. Testing someone’s normal DNA can now help guide treatment since we have newer therapies against germline DNA changes. It can also tell us about future cancer risks and how to best manage those risks, as well as tell us about potential cancer risks for someone’s blood relatives. It is also important to remember that when testing is done on tumor and/or germline DNA, it may also uncover potential germline mutations found in the normal cells that are unexpected and not related to someone’s cancer. However, this information is still potentially important to help guide future cancer risks and management and to inform potential inherited cancer risks for family members.




ICARE Social Media Post February 2020

Ovarian Cancer Risks in BRCA1/2

The risk of ovarian cancer is raised in women with BRCA1/2 mutations. Recent findings suggest that higher body mass index (BMI) may further raise the risk of ovarian cancer in premenopausal BRCA1/2 carriers.

Note that all women with BRCA1/2 mutations are at high risk for ovarian cancer, and should follow current National Comprehensive Cancer Network (NCCN) management guidelines which recommend risk-reducing salpingo-oophorectomy (removal of ovaries and fallopian tubes) between age 35 and 40 for BRCA1 carriers and between age 40 and 45 for BRCA2 carriers, regardless of BMI.

Check out the article at https://www.ncbi.nlm.nih.gov/pubmed/31213659 and NCCN guidelines by creating a FREE account at https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf.




ICARE Social Media Post February 2020

Characteristics and Patterns of Spread for BRCA-associated Breast Cancers

BRCA1/2 have distinct characteristics and patterns of spread.

A recent study evaluated the characteristics of BRCA1/2 carriers and found that 73% ofBRCA1-associated breast cancers were triple negative; and 72% of BRCA2-associated breast cancers were hormone receptor positive. There were also distinct pattern of spread of breast cancer, with BRCA1 carriers more likely to experience lung and distant lymph node metastasis, while BRCA2 carriers were more likely to experience central nervous system and bone metastasis.

This information may help to guide care among women with BRCA1/2 mutations with breast cancer.

To read the full article visit https://www.ncbi.nlm.nih.gov/pubmed/31581314




ICARE Social Media Post February 2020

Differences in Pancreatic Cancer Screening Recommendations from the National Comprehensive Cancer Network (NCCN) and the International Cancer of the Pancreas Screening (CAPS) Consortium

The National Comprehensive Cancer Network (NCCN) and the International Cancer of the Pancreas Screening (CAPS) Consortium recently updated pancreatic cancer screening recommendations. However, there are some differences between these recommendations. Specifically, screening with annual MRI/magnetic retrograde cholangiopancreatography (MRCP) and/or endoscopic ultrasound (EUS) is recommended as follows for NCCN versus CAPS:

STK11 regardless of family history:

  • NCCN: Consider screening beginning at age 30-35
  • CAPS: Consider screening beginning at age 40

CDKN2A regardless of family history:

  • NCCN: Consider screening beginning at age 40
  • CAPS: Consider screening beginning at age 40

BRCA1/2, PALB2, ATM, MLH1, MSH2 & MSH6 and at least one affected relative with pancreatic cancer:

  • NCCN: If first- or second-degree relative affected, consider screening beginning at age 50
  • CAPS: If first-degree relative affected, consider screening beginning at age 45-50

EPCAM & TP53:

  • NCCN: If first- or second-degree relative affected, consider screening beginning at age 50
  • CAPS: Not included in screening recommendations

Check out NCCN guidelines by creating a FREE account at https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf

Check out the full CAPS article at https://www.ncbi.nlm.nih.gov/pubmed/31672839




ICARE Social Media Post February 2020

Updated Pancreatic Cancer Screening Guidelines through the International Cancer of the Pancreas Screening (CAPS) Consortium

The International Cancer of the Pancreas Screening (CAPS) Consortium recently published updated pancreatic cancer screening recommendations. The recommendations include:

  • Screening with MRI/magnetic retrograde cholangiopancreaography (MRCP) and/or endoscopic ultrasound (EUS)

The screening was recommended for the following individuals:

  • CDKN2A and STK11 mutation carriers starting at age 40
  • BRCA1/2, ATM, PALB2, MLH1, and MSH2 mutation carriers (if they have at least one first-degree relative with pancreatic cancer) starting at age 45-50 or 10 years younger than the youngest affected relative

Check out the full article at https://www.ncbi.nlm.nih.gov/pubmed/31672839

 

These guidelines differ from current NCCN Pancreatic Cancer Screening Guidelines as follows:

STK11:

  • CAPS: Consider screening beginning at age 40
  • NCCN: Consider screening beginning at age 30-35

MSH6, EPCAM, TP53:

  • CAPS: Not included
  • NCCN: Consider screening beginning at age 50

CDKN2A, BRCA1, BRCA2, PALB2, ATM, MLH1, MSH2, MSH6:

  • Screening recommendations remain the same as CAPS

Check out NCCN guidelines by creating a FREE account at https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf.




ICARE Social Media Post January 2020

Racial Disparities in Genetic Testing for Women with Ovarian Cancer

Women of non-European ancestry diagnosed with ovarian cancer have lower rates of referral for genetic testing despite current national guidelines stating ALL women with ovarian cancer and/or a close-blood relative with ovarian cancer should be offered genetic counseling and testing.

One study reported that only 1/3 of Black, Latina, and Asian women were referred for genetic counseling following an ovarian cancer diagnosis, compared to two-third of White women. This study highlights the need to develop strategies such that genetic testing is used across all populations, including racial/ethnic minorities.

Check out the article at: https://www.sciencedirect.com/science/article/pii/S0090825817314555.




ICARE Social Media Post January 2020

Women with BRCA1/2: Risk-reducing Mastectomy versus Screening

In a study of 5000 healthy female BRCA1/2 carriers (without a breast cancer diagnosis):

  • BRCA1 carriers: after an average of over 10 years follow-up, survival was higher in those who had bilateral mastectomy (99.7%) compared to those who had breast screening through mammograms and breast MRIs (93%).
  • BRCA2 carriers: no significant differences were seen between those who had bilateral mastectomy versus screening.

Although the results of this study provide additional information that may be useful to BRCA carriers, it remains important to remember that cancer risk management decisions are a personal decision. It is important to be aware of the information available to make an informed decision, with guidance from your healthcare provider.

Check out the article at: https://www.ncbi.nlm.nih.gov/pubmed/31302855




ICARE Social Media Post January 2020

Celebrating 10 Years of ICARE

 

Happy New Year! 2020 represents a decade for ICARE

We are celebrating 10 years of research, education, and engagement, through which we have enrolled nearly 3500 participants, including over 2000 gene mutation carriers, disseminated 15 newsletters, led and collaborated on multiple research projects, and impacted individuals affected by inherited cancer predisposition all over the world.

Let’s take a quick look at what’s happened in the last decade:

2010ICARE was launched.

2012 – First commercially available gene panel test for inherited cancer became available, and ICARE reached 1000 study participants! Cost of testing just for BRCA1 and BRCA2 was over $4000.

2013 –The Supreme Court invalidated the BRCA patent which allowed expanded use of multi-gene panel testing as the BRCA genes could then be added to the panel tests.

2015 – FDA approved the use of PARP inhibitors for BRCA carriers with ovarian cancer which improved treatment options.

2016ICARE reached 1000 BRCA carriers and 2000 study participants!

2017 – The FDA approved immunotherapy treatment for mismatch repair-deficient cancers, which was an important advance for individuals with Lynch syndrome.

2019ICARE reached 3000 study participants!

2020 – Ongoing discovery of new cancer genes and improved technology continues to drive cost of genetic tests down to as low as $250 and lower!

Thank you for your continued support in helping us fulfill our mission to end the cycle of inherited cancer through research, education, and engagement!




ICARE Social Media Post January 2020

Advances in Treatment for Pancreatic Cancer in BRCA Carriers

The FDA approved the use of olaparib, a PARP inhibitor, as first-line maintenance treatment in BRCA1/2 carriers with metastatic, platinum-sensitive, pancreatic cancer.

Platinum-sensitive cancer is a cancer that responds to treatment with drugs that contain the metal platinum, such as carboplatin or cisplatin. Olaparib showed to nearly double the progression-free survival in BRCA1/2 carriers with metastatic pancreatic cancer.

The recent FDA approval to use olaparib as first-line maintenance treatment for BRCA carriers with metastatic pancreatic cancer represents another strategy to improve treatment of pancreatic cancer. It also demonstrates the importance of genetic testing for ALL patients with pancreatic cancer (because it will tell us who has a BRCA mutation, which may then make them eligible for PARP inhibitor treatment).

Check out the articles at: https://www.ncbi.nlm.nih.gov/pubmed/?term=Maintenance+Olaparib+for+Germline+BRCA-Mutated+Metastatic+Pancreatic+Cancer

-OR-

https://www.healio.com/hematology-oncology/gastrointestinal-cancer/news/online/%7B3235fd91-3983-444f-b51e-39a111619a12%7D/maintenance-olaparib-significantly-delays-progression-of-brca–mutated-pancreatic-cancer




ICARE Social Media Post December 2019

Evaluation of PARP Inhibitors in BRCA-Associated Prostate Cancer

The FDA granted breakthrough therapy designation to niraparib (a PARP inhibitor) for the treatment of men with BRCA1/2 positive, metastatic castration-resistant, and heavily pre-treated prostate cancer.

Results from a recent study show a 63% complete response rate in men with BRCA1/2 positive, metastatic castration-resistant prostate cancer treated with niraparib compared to 17% in the non- BRCA group.

Previously, niraparib was approved for ovarian cancer. This treatment can help address lack of treatment options for men with BRCA1/2 positive, metastatic castration-resistant prostate cancer.

Check out the articles at https://www.cancernetwork.com/fda/fda-grants-breakthrough-therapy-designation-niraparib-mcrpc and https://www.healio.com/hematology-oncology/prostate-cancer/news/online/%7B22878907-82bd-408e-b99f-b51c50d8c467%7D/fda-grants-breakthrough-therapy-designation-to-zejula-for-prostate-cancer-subtype.




ICARE Publication December 2019

Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG)

No abstract available

Pal T, et al. Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2020 Apr;22(4):681-685. Epub 2019 Dec 13. PMID: 33455826.




ICARE Social Media Post December 2019

Patient Reported Outcomes In A Study of PARP Inhibitors in BRCA Carriers with Metastatic Breast Cancer

Did you know? PROs are impacting treatment advances in metastatic breast cancer. Olaparib increased progression-free survival among BRCA carriers with metastatic HER2- breast cancer. Thanks to patient reported outcomes, a new study now suggests it also improved patients’ quality of life!

Check it out the new article published in October 2019 directly at https://www.ncbi.nlm.nih.gov/pubmed/31446213!




ICARE Social Media Post December 2019

Updates to National Comprehensive Cancer Network (NCCN) Genetic/Familial Breast, Ovarian, and Pancreatic Guidelines (V1.2020)

We are excited to share the latest version of the NCCN Genetic/Familial Breast, Ovarian and Pancreatic Guidelines (V1.2020), which were just updated. Some of the changes made include:

  • PALB2 was added as a high penetrance gene (similar to BRCA1, BRCA2, CDH1, PTEN and TP53)
  • It is appropriate to consider risk reducing mastectomy for cancer risk management (as well as high risk screening through mammograms and MRIs).
  • The age at which screening for prostate cancer among men with a BRCA2 mutation was lowered from 45 to 40.
  • Pancreatic cancer screening:
    • Individuals with STK11 (which leads to Peutz-Jeghers Syndrome) or CDKN2A mutations has been added
    • ONLY a consideration in patients with a mutation in BRCA1/2, ATM, MLH1, MSH2, EPCAM, PALB2, and TP53 IF there is a close family member (first or second degree relative on the same side of the family) with pancreatic cancer
  • The guidelines also outline situations in which there is a very low chance of finding a mutation (i.e., pathogenic/likely pathogenic variant).

To see the full version of the guidelines, go to nccn.org, where they will ask you to create a username and password (which anyone can do), after which you will be able to view whichever guidelines you want. Check it out at https://www.nccn.org/about/news/newsinfo.aspx?NewsID=1790!




ICARE Social Media Post November 2019

High Frequency of BRCA in Unselected Women with Metastatic Breast Cancer

Did you know? National practice guidelines currently recommend ALL women with metastatic (HER2-) breast cancer to get genetic testing for inherited cancer (including BRCA1/2 testing), because it can guide eligibility for treatment with PARP inhibitors.

A new study led by our colleague at the Vanderbilt-Ingram Cancer Center, Dr. Ben Park, suggests that more women with metastatic breast cancer have BRCA1/2 mutations than previously thought. In fact, of the 100 women with metastatic breast cancer tested through this study, 6% had BRCA1/2 mutations!

Findings from this study highlight the importance of genetic testing for ALL women with metastatic breast cancer to help guide their treatment, AND further guide risk management for themselves and their at-risk family members.

Check out the study at the following link: https://www.ncbi.nlm.nih.gov/pubmed/31465090




ICARE Publication November 2019

Impact of Genetic Testing on Risk-Management Behavior of Black Breast Cancer Survivors: A Longitudinal, Observational Study

Abstract

BackgroundBlack women are overrepresented among premenopausal breast cancer (BC) survivors. These patients warrant genetic testing (GT) followed by risk-reducing behaviors. This study documented patterns and predictors of cancer risk-management behaviors among young black BC survivors after GT.

MethodsBlack women (n = 143) with a diagnosis of BC at the age of 50 years or younger received GT. At 1 year after GT, participants reported receipt of risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, mammogram, breast magnetic resonance imaging (MRI), CA125 test, and transvaginal/pelvic ultrasound. Logistic regression was used to examine predictors of BC risk management (risk-reducing mastectomy or breast MRI) and ovarian cancer risk management (risk-reducing salpingo-oophorectomy, CA125 test, or transvaginal/pelvic ultrasound).

ResultsOf the study participants, 16 (11%) were BRCA1/2-positive, 43 (30%) had a variant of uncertain significance, and 84 (59%) were negative. During the 12 months after GT, no women received risk-reducing mastectomy. The majority (93%) received a mammogram, and a smaller proportion received breast MRI (33%), risk-reducing salpingo-oophorectomy (10%), CA125 test (11%), or transvaginal/pelvic ultrasound (34%). Longer time since the BC diagnosis predicted lower likelihood of BC risk management (odds ratio [OR] 0.54). BRCA1/2 carrier status (OR 4.57), greater perceived risk of recurrence (OR 8.03), and more hereditary breast and ovarian cancer knowledge (OR 1.37) predicted greater likelihood of ovarian cancer risk management.

ConclusionsYoung black BC survivors appropriately received mammograms and ovarian cancer risk management based on their BRCA1/2 test result. However, the low usage of MRI among BRCA1/2 carriers contrasts with national guidelines. Future research should examine barriers to MRI among black BC survivors. Finally, modifiable variables predicting risk management after GT were identified, providing implications for future interventions.

Conley C, et al. Impact of Genetic Testing on Risk-Management Behavior of Black Breast Cancer Survivors: A Longitudinal, Observational Study. Ann Surg Oncol. 2020 May;27(5):1659-1670. Epub 2019 Nov 1. PMID: 31677107.




ICARE Social Media Post October 2019

Lifestyle Factors Associated with Familial and Inherited Breast Cancer Risks

Body mass index (BMI) is an indicator of fat content in the body. A lower body mass index may reduce breast cancer risk in women, including those with a family history of breast cancer. However, a new study reported that higher BMI also increases breast cancer risk in the general population and those with a family history of breast cancer after menopause.

Maintaining a healthy weight throughout adulthood is important in ALL women, including those with a family history of breast cancer. These findings were recently published in Breast Cancer Research (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215632/)

2) A new study suggests that regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) might also lower breast cancer risk in women in BRCA1/2 carriers AND those with family history of breast cancer.

These findings were recently published in Breast Cancer Research (https://breast-cancer-research.biomedcentral.com/track/pdf/10.1186/s13058-019-1135-y)




ICARE Social Media Post October 2019

Physical Activity Associated with Familial and Inherited Breast Cancer Risks

BRCA1/2 carriers may benefit from physical activity to reduce breast cancer risks, just like women in the general population! We know that women in the general population benefit from physical activity to reduce their breast cancer risk, but a recent study showed that this benefit also extends to those with a BRCA1/2 mutation and those with a family history of breast cancer.

This study showed that breast cancer risk could be lowered by 20% for those with the highest physical activity levels. This risk reduction was equally seen among women in the general population, those with familial risk (family history of breast cancer), and those with a BRCA1/2 mutation.

Physical activity does not have to be painful and boring, there are many fun ways you can stay active such as walking in your favorite park, attending your favorite yoga class, chasing after your grandchildren, and walking a race for a good cause with your friends and family!

These findings were recently published in Cancer Research (https://www.ncbi.nlm.nih.gov/pubmed/31578201)




ICARE Social Media Post October 2019

BRCA Testing In Black Women

Did you know? Although BRCA testing has been around for over TWO decades, not all populations have benefitted equally from testing. In fact, our previous research has shown that black patients are less aware of BUT interested in genetic testing…when they know about it.

In addition, healthcare providers are less likely to identify and suggest BRCA testing among young black women with breast cancer compared to white women. What’s concerning is that black women are more likely to get breast cancer early and/or triple-negative disease, which are both hallmarks for inherited disease.

Check it out at https://bgreatinitiative.inheritedcancer.net/newsletters/




ICARE Social Media Post October 2019

Advances in Treatment for Advanced Breast Cancer in BRCA Carriers

Monotherapy with PARP inhibitors is FDA-approved for patients with metastatic breast cancer with BRCA mutations. BUT, does adding additional drugs (called ‘combination therapy’) help?

In BRCA carriers with metastatic breast cancer, the combination of veliparib AND chemotherapy with platinum-based agents (carboplatin) and taxanes (paclitaxel) led to a longer duration of progression free survival (disease that did not progress), compared to those treated with ONLY chemotherapy. The duration of progression free survival was DOUBLE with veliparib/chemotherapy 3 years after treatment.

Additional information can be found at ESMO 2019’s BROCADE 3 abstract.




ICARE Social Media Post October 2019

Advances in Early Stage Breast Cancer Treatment for BRCA Carriers

New benefits from a PARP inhibitor, talazoparib, among BRCA carriers with early stage breast cancer. The current FDA approvals for the use of PARP inhibitors is limited to women with metastatic (stage IV) breast cancer. These drugs are being tested in early stage breast cancer to shrink down the tumor (called neoadjuvant treatment) before surgery to remove it.

Specifically, 6 months of neoadjuvant talazoparib monotherapy (treatment with only talazoparib) resulted in significantly improved rates of complete response in patients with operable (stage I-III) breast cancer.

Check out the full article at: https://pubmed.ncbi.nlm.nih.gov/31461380/

You can also look for other treatment advances in BRCA carriers in our newsletters at https://inheritedcancer.net/newsletters/.




ICARE Social Media Post October 2019

Male Breast Cancer Risk

Did you know? Beyonce’s father, Matthew Knowles, was diagnosed with breast cancer. He states, “we used to think this was only an issue for women, but this is male or female.” According to CBS news, “he is hoping that sharing his story as man with breast cancer will shine a light on the risk men can face.”

Surprisingly, less than 20% of women diagnosed with breast cancer who are at high risk for a BRCA mutation are tested. Even lower rates of genetic testing are seen among African Americans, who are less aware of their risk for a BRCA mutation.

Let’s talk facts. All men with breast cancer should be offered BRCA testing. 6-8% of men with breast cancer will have a BRCA2 mutation. Matthew’s children have a 50/50 chance of inheriting this BRCA2 mutation. Women with the mutation, have a 60-70% risk to develop breast cancer. The BRCA2 gene raises the chance for ovarian cancer in women, aggressive prostate cancer in men and pancreatic cancer in both sexes. See our previous post about new targeted treatment options for cancer patients with a BRCA2 mutation.

Genetic testing for inherited cancer genes (such as BRCA1/2) can be done through a simple blood or saliva sample. Detecting a mutation allows people to be proactive about their health by finding cancer early or preventing it all together.  Check out resources to ‘end the cycle of inherited cancer through research, education, and engagement’ at http://inheritedcancer.net/




ICARE Newsletter Summer 2019

Ask the Expert

The following question was addressed by Gillian Hooker, PhD, ScM, LCGC, who is the president-elect for the National Society of Genetic Counselors, Adjunct Associate Professor in the Division of Genetic Medicine at the Vanderbilt University Medical Center, and the Vice President of Clinical Development for Concert Genetics in Nashville, TN.

Q. Why was the BRCA1/2 mutation detected through genetic testing ordered by my healthcare provider but not found on my 23andMe® genetic test?

A. This is not unexpected. There are thousands of different mutations in the BRCA1 and BRCA2 (BRCA1/2) genes found among families with inherited cancers. When testing is ordered by a healthcare provider, the vast majority of mutations in these genes can be detected if they are there.  However, BRCA1/2 at-home genetic testing done by 23andMe® looks for only 3 specific mutations in the BRCA1/2 genes found mostly in people of Ashkenazi Jewish descent. This testing does not look for the thousands of other mutations that have been found in the BRCA1/2  In fact, a study published last year looked at 49 different patients who learned from at-home testing that they had mutations.1 When these samples were tested again after a healthcare provider ordered the test, 40% of the mutations were not found (i.e., they were ‘false positives’).  Other “mutations” were present, but turned out to be benign, non-harmful genetic changes after further inspection. These findings highlight the shortcomings of at home genetic testing, and the potential for miscommunication, misinformation, and distress as eloquently articulated in a recent article by Dorothy Pomerantz.2 We recommend reaching out to your doctor or a genetic counselor if you have questions about these tests.

1Tandy-Connors, et al. Genet Med. 2018 Dec. PMID: 29565420.
2Pomerantz D. “23andMe had devastating news about my health. I wish a person had delivered it.” Stat News, available at: https://www.statnews.com/2019/08/08/23andme-genetic-test-revealed-high-cancer-risk/




ICARE Newsletter Summer 2019

Ovarian Cancer Treatment Advances for BRCA1/2 Carriers

A recently reported study of women with ovarian cancer and homologous recombination deficiency (HRD) who received a PARP inhibitor (niraparib) as fourth line or later treatment showed potential clinical benefit. Specifically, median overall survival after treatment was 19 months in the HRD-positive group (including those with BRCA1/2 mutations) compared to 15.5 months in the HRD-negative group. In fact, the subgroup with BRCA1/2 mutations had a median overall survival of 26 months. These results suggest possible expansion for use of this class of drugs beyond those with BRCA1/2 mutations to a broader patient population with HRD-positive ovarian cancer.

Moore, et al. Lancet Oncol. 2019 May. PMID 30948273.




ICARE Newsletter Summer 2019

New Information About Cancer Risks for Inherited Cancer Genes: BRCA1/2

Looking at pregnancy history and breast cancer risk, a recent study of almost 8,000 women with BRCA1/2 mutations evaluated breast cancer risks related to pregnancy.1 Findings suggested the overall number of pregnancies was not associated with breast cancer risk in BRCA1 carriers; however, BRCA1 carriers with one pregnancy were at higher risk for breast cancer when compared to those with no pregnancies or more than one pregnancy. In contrast, among BRCA2 carriers, more pregnancies were associated with a lower breast cancer risk. Additionally, longer duration of breastfeeding in BRCA1 carriers lowered breast cancer risks. Looking at risks of contralateral breast cancer after removal of the ovaries, in a study of over 2,000 women with a BRCA1 or BRCA2 mutation and almost 10 years of follow-up, results suggested that removal of the ovaries did not reduce the chance of developing a second new breast cancer.2 This finding did not change with type of BRCA1/2 mutation or age at diagnosis of the first breast cancer. Overall, these findings suggest that removing the ovaries in BRCA1/2 carriers with breast cancer may not reduce their risk for developing another breast cancer. Looking at Non-Hodgkin lymphoma risks, in a study of pediatric cancer survivors, results suggested that children and adolescents with a BRCA2 mutation may have a higher risk for non-Hodgkin lymphoma, with a significant association (Odds Ratio of 5; 95% Confidence Interval: 2.1-10.2).3 These findings contribute to refining cancer risks among those with BRCA1/2 mutations and require confirmation through other studies.

 1Terry, et al. JNCI Cancer Spectr. 2018 Dec. PMID: 30873510.
2Kotsopoulos, et al. Breast Cancer Res Treat. 2019 Jun. PMID: 30756284.
3Wang, et al. JAMA Oncol. 2019 Jul. PMID: 31343663.




ICARE Newsletter Summer 2019

Pancreatic Cancer Treatment Advances for BRCA1/2 Carriers

Results from a clinical trial of individuals with a BRCA1/2 mutation and pancreatic cancer showed that patients who received a PARP inhibitor (olaparib) for maintenance treatment had almost half the risk of their disease progressing when compared to receiving a placebo.1 In fact, after 2 years, 22.1% of patients who received olaparib had no disease progression compared to 9.6% of those receiving a placebo.1 In October 2018, Lynparza (olaparib) received orphan drug designation for pancreatic cancer through the U.S. Food and Drug Administration. Another study of a PARP inhibitor called rucaparib, presented at the 2019 AACR meeting, showed that BRCA1/2 or PALB2 carriers with advanced, platinum-sensitive, pancreatic cancer seemed to benefit from this maintenance treatment.2 In fact, of the 19 patients assessed so far, one had a complete response and six had a partial response to the treatment.2 These results remain preliminary and require more proof that they are true, but represent another possible treatment advance for those with pancreatic cancer and BRCA1/2 or PALB2 mutations. These results also highlight the importance for both germline (inherited) and tumor (somatic) testing among patients with pancreatic cancer.

1Golan, et al. N Engl J Med. 2019 July. PMID 31157963.
2Reiss Binder, et al. Abstract CT234. AACR Annual Meeting, presented 2019 April.




ICARE Newsletter Summer 2019

Expansion of Criteria for BRCA1/2 Testing through the USPSTF

The U.S. Preventive Services Task Force (USPSTF) came out with new genetic testing guidelines for the BRCA1/2 genes, which has garnered substantial media attention. This task force consists of a team of primary care and preventive medicine healthcare experts to lower the chance of a conflict of interest  (which is also the reason that subspecialty providers who practice in the area of clinical cancer genetics were excluded from this group, but who may be consulted to provide input).  For the current guideline, essentially a three-step process was included: 1) a brief risk assessment for BRCA1/2 risk by primary care providers with a validated tool; 2) referral to genetic counseling if positive; and 3) BRCA1/2 testing if indicated.

A substantial update to the guideline is that it now covers more women at-risk for a BRCA1/2 mutation.  Specifically, guidelines now include women with a history of breast, ovarian, fallopian tube, and peritoneal cancer who are disease-free, as well as those with ancestry prone to BRCA1/2 mutations, such as Ashkenazi Jewish women.  Some of the items that were not addressed include: 1) other cancers associated with the BRCA1/2 genes, including male breast cancer, prostate cancer, or pancreatic cancer; 2) other inherited breast or ovarian cancer genes (this is especially relevant as  most providers are not just testing for the BRCA1/2 genes, but other genes as well through multi-gene panel tests); 3) existing disparities in testing across racial/ethnic groups, and how these new guidelines may affect existing disparities; and 4) lack of accounting for some of the subtle nuances of treating those with a BRCA1 or BRCA2 mutation by outlining the differences in type of breast cancer that each primarily predisposes someone to (i.e., triple negative breast cancer) and providing evidence to support hormone receptor blockers for prevention.

 

 

 

 

 

 

 

 

 

 

 

US Preventive Services Task Force, Owens et al. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2019 Aug. PMID: 31429903. Available at: https://jamanetwork.com/journals/jama/fullarticle/2748515




ICARE Newsletter Summer 2019

Prostate Cancer Treatment Advances for BRCA1/2 Carriers

There is now information to suggest that identifying inherited mutations in DNA repair genes, such as BRCA1/2 and other genes, in men with metastatic prostate cancer may open doors for other treatment options. Results of a phase 2 clinical trial among men with metastatic and heavily pre-treated prostate cancer were presented at the American Society of Clinical Oncology 2019 meeting.1 Mateo and colleagues found that treatment with a PARP inhibitor (olaparib) was promising among those with BRCA1/2 mutations (24 of 30 patients) and PALB2 mutations (4 of 7 patients), while patients with other inherited genes also showed some response.1 Another recent study suggested that men with metastatic prostate cancer and a BRCA2 mutation who received androgen blockers for their initial treatment had better outcomes compared with those who received taxanes.2 This suggests that BRCA2 status may guide initial treatments among metastatic prostate cancer patients.2

 1Mateo, et al. J Clin Oncol. 2019 May. DOI: 10.1200/JCO.2019.37.15_suppl.5005.
 2Castro, et al. J Clin Oncol. 2019 Feb. PMID 30625039.




ICARE Publication April 2019

International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation

Abstract

BackgroundWomen with a BRCA1 or BRCA2 mutation face high risks of breast and ovarian cancer. In the current study, we report on uptake of cancer screening and risk-reduction options in a cohort of BRCA mutation carriers from ten countries over two time periods (1995 to 2008 and 2009 to 2017).

MethodsEligible subjects were identified from an international database of female BRCA mutation carriers and included women from 59 centres from ten countries. Subjects completed a questionnaire at the time of genetic testing, which included past use of cancer prevention options and screening tests. Biennial follow-up questionnaires were administered.

ResultsSix-thousand two-hundred and twenty-three women were followed for a mean of 7.5 years. The mean age at last follow-up was 52.1 years (27-96 years) and 42.3% of the women had a prior diagnosis of breast cancer. In all, 27.8% had a prophylactic bilateral mastectomy and 64.7% had a BSO. Screening with breast MRI increased from 70% before 2009 to 81% at or after 2009. There were significant differences in uptake of all options by country.

ConclusionFor women who received genetic testing more recently, uptake of prophylactic mastectomy and breast MRI is significantly higher than those who received genetic testing more than 10 years ago. However, uptake of both BSO and breast MRI is not optimal, and interventions to increase uptake are needed.

Metcalfe K, et al. International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation. Br J Cancer. 2019 Jul;121(1):15-21. Epub 2019 Apr 11. PMID: 30971774.




ICARE Publication April 2019

A randomized controlled intervention to promote readiness to genetic counseling for breast cancer survivors

Abstract

ObjectiveBreast cancer (BC) survivors with a genetic mutation are at higher risk for subsequent cancer; knowing genetic risk status could help survivors make decisions about follow-up screening. Uptake of genetic counseling and testing (GC/GT) to determine BRCA status is low among high risk BC survivors. This study assessed feasibility, acceptability, and preliminary efficacy of a newly developed psychoeducational intervention (PEI) for GC/GT.

MethodsHigh risk BC survivors (N = 119) completed a baseline questionnaire and were randomized to the intervention (PEI video/booklet) or control (factsheet) group. Follow-up questionnaires were completed 2 weeks after baseline (T2), and 4 months after T2 (T3). We analyzed recruitment, retention (feasibility), whether the participant viewed study materials (acceptability), intent to get GC/GT (efficacy), and psychosocial outcomes (eg, perceived risk, Impact of Events Scale [IES]). t tests or chi-square tests identified differences between intervention groups at baseline. Mixed models examined main effects of group, time, and group-by-time interactions.

ResultsGroups were similar on demographic characteristics (P ≥ .05). Of participants who completed the baseline questionnaire, 91% followed through to study completion and 92% viewed study materials. A higher percentage of participants in the intervention group moved toward GC/GT (28% vs 8%; P = .027). Mixed models demonstrated significant group-by-time interactions for perceived risk (P = .029), IES (P = .027), and IES avoidance subscale (P = .012).

ConclusionsThe PEI was feasible, acceptable, and efficacious. Women in the intervention group reported greater intentions to pursue GC, greater perceived risk, and decreased avoidance. Future studies should seek to first identify system-level barriers and facilitators before aiming to address individual-level barriers.

Kasting M, et al. A randomized controlled intervention to promote readiness to genetic counseling for breast cancer survivors. Psychooncology. 2019 May;28(5):980-988. Epub 2019 Apr 11. PMID: 30883986




ICARE Newsletter Winter 2019

Basal Cell Cancers May Be a Risk Factor to Predict Inherited Cancer Predisposition

An interesting area of progress to identify individuals with inherited risks included a study of over 13,000 individuals with six or more basal cell cancers (BCC) evaluated through a claims database. Results indicated ~20% of these individuals had a germline mutation in a DNA repair gene, including BRCA1/2, PALB2, and the Lynch syndrome genes, among others. Furthermore, these individuals had over a 3-fold risk of other malignancies. These findings suggest that frequent BCC may represent a marker to identify potential inherited cancer risk.

Cho HG, et al. JCI Insight. 2018 Aug 9. PMID: 30089731.




ICARE Newsletter Winter 2019

New Research and Approvals of PARP Inhibitor Drugs to Treat Prostate Cancer in BRCA Carriers

Treatment among patients with metastatic castration-resistant prostate cancer: A PARP inhibitor (rucaparib) was granted a breakthrough therapy designation in October 2018 for monotherapy (i.e., sole treatment) among men with metastatic castration-resistant prostate cancer (with a BRCA1/2 mutation) who have received at least one prior androgen receptor-directed treatment and taxane-based chemotherapy. This designation was granted based on results of the phase II TRITON2 study, some results of which have been presented at national meeting, but not yet published.




ICARE Newsletter Winter 2019

Ask the Expert

The following question was addressed by Georgia Wiesner, MD, MS, a nationally renowned clinical cancer geneticist, who is an Ingram Professor of Cancer Research, Professor of Medicine in the Division of Genetic Medicine, and the Director of the Clinical and Translational Hereditary Cancer Program for the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

Q. What are the reproductive options for people with a BRCA mutation who do not want to pass their mutation on to their future children?

A. It is important to realize that pregnancy can be achieved without worry about passing on a gene mutation to future

generations. There are several options for couples, including adoption, gamete (egg or sperm) donation, and preimplantation genetic diagnosis (PGD) with in vitro fertilization (IVF). PGD begins with the normal process of IVF including egg retrieval and fertilization of the egg in a laboratory. When the fertilized egg (or “embryo”) reaches the 8-cell stage, one cell is removed to test it for the familial mutation. Then, embryos without the mutation can be selectively implanted using standard IVF procedures. However, the process of PGD with IVF requires confirmation prior to any procedure so that the lab can unambiguously detect the familial mutation. It can also be costly and may not be covered by insurance and involves invasive procedures. Therefore, couples considering PGD should be counseled by an experienced provider prior to any attempts to achieve a pregnancy. This process may also be relevant to individuals with other inherited gene mutations.




ICARE Newsletter Winter 2019

New Research and Approvals of PARP Inhibitor Drugs to Treat Breast Cancer in BRCA Carriers

Treatment among patients with advanced or metastatic breast cancer: A PARP inhibitor (talazoparib) was approved by the FDA on October 16, 2018 for BRCA carriers with HER2-negative locally advanced or metastatic breast cancer, based on results of the EMBRACA trial outlined in the last ICARE newsletter.

Litton JK, et al. N Engl J Med. 2018 Aug 23. PMID: 30110579.




ICARE Newsletter Winter 2019

Refining Treatment for Aggressive Prostate Cancer in Men with BRCA2

A recent study reported that a large proportion of men with aggressive prostate cancer have inherited cancer gene mutations. Specifically, among 400 patients with castration-resistant prostate cancer, 16.2% had a germline mutation in a DNA damage repair gene, including 3% with a BRCA2 mutation. Among BRCA2 carriers, survival was 17.4 months, which was much lower than the 33.2 months observed among non-carriers. Furthermore, the subset of BRCA2 carriers who received first-line treatment with abiraterone or enzalutamide had better outcomes than those who received taxanes. Consequently, these findings suggest that determination of BRCA2 status may help to guide initial treatment of metastatic prostate cancer among BRCA2 carriers, although additional studies are needed to confirm these results.

Castro E, et al. J Clin Oncol. 2019 Jan 9. PMID: 30625039.




ICARE Newsletter Winter 2019

New Research and Approvals of PARP Inhibitor Drugs to Treat Ovarian Cancer in BRCA Carriers

First line maintenance treatment among patients newly diagnosed with advanced ovarian cancer: The results of a trial using a PARP inhibitor (olaparib) as maintenance treatment among ovarian cancer patients with advanced disease, a BRCA mutation, and complete or partial response to platinum-based chemotherapy showed that survival at 3 years was 60% among those who got the drug versus 27% among those who did not. Investigators concluded that among those with successful first-line chemotherapy, “The use of maintenance therapy with olaparib provided a substantial benefit among women with newly diagnosed advanced ovarian cancer and a BRCA mutation, with a 70% lower risk of disease progression or death with olaparib than with placebo.” Soon after publication of these results, on December 19, 2018, the FDA approved olaparib for maintenance treatment of BRCA-mutation advanced ovarian cancer.

Moore K, et al. N Engl J Med. 2018 Dec 27. PMID: 30345884.




ICARE Newsletter Winter 2019

Testing Interpretation and Variant Reclassification

Results of germline genetic testing generally yield three types of test results: Deleterious (positive), Negative (no mutation detected), and Variant of Uncertain Significance (VUS). As more genes are tested, the chance for a positive result goes up, as does the chance of receiving a VUS result.1 VUS results tell us that it remains uncertain whether the test result is positive or negative. A recently published study demonstrated that most VUS results are downgraded to negative over time.2 Specifically, of more than 25,000 VUS results reported through a single testing laboratory, about a quarter were reclassified over time, of which over 90% were downgraded to negative (benign or likely benign). Information from this study is important when counseling patients with VUS results, informing them that most VUS results that are reclassified are downgraded, and explaining that VUS results are generally not used to direct medical care. On the topic of interpretation of genetic test results, another paper reported on a novel method to better classify BRCA1 mutations as positive or negative, through tracking how cells with specific BRCA1 changes, growing in lab dishes, respond.3 These types of efforts are important to better classify gene changes identified through genetic testing, and hopefully will serve to reduce the number of VUS results received by patients in the future. Finally, as knowledge expands, it becomes more important to make interpretation of genetic test information widely available for it to be maximally used to improve patient care. To that effect, a recent report outlined a global resource that includes data on more than 20,000 unique BRCA1 and BRCA2 variants, called the “BRCA Exchange”.4 Over 6,100 variants in this database have been classified by an expert panel, and approximately 3,700 are established to be positive (i.e., they raise the risk for cancer). This dataset was set up to pull in information from existing clinical databases, including the Breast Cancer Information Core (BIC), ClinVar, and the Leiden Open Variation Database, as well as other databases and data worldwide. It has a single-point-of-access website (https://brcaexchange.org/) and serves to demonstrate that this type of widespread data sharing across multiple entities is possible for other inherited cancer genes and genes associated with other diseases.

1Kurian AW, et al. JAMA. 2018 Aug 1. PMID: 29801090.
2Mersch J, et al. JAMA. 2018 Sept 25. PMID: 30264118.
3Findlay GM, et al. Nature. 2018 Oct. PMID: 30209399.
4Cline MS, et al. PLoS Genet. 2018 Dec 26. PMID: 30586411.




ICARE Newsletter Winter 2019

New Online Risk Calculator to More Accurately Predict Breast Cancer Risk

Prediction of breast cancer risk is important to identify those at highest and lowest risks, to help guide screening. A previously developed risk algorithm called Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) was recently extended to include truncating mutations in the BRCA genes, PALB2, CHEK2, and ATM. This online risk calculator could help healthcare providers more accurately predict breast cancer risks in patients. To access the risk calculator, please visit: https://ccge.medschl.cam.ac.uk/boadicea/.

Lee A, et al. Genet Med. 2019 Jan 15. PMID: 30643217.




ICARE Newsletter Summer 2018

The Role of Inherited Genes Increasingly Recognized in Pancreatic Cancer

A number of recent studies have suggested that a substantial number of individuals with pancreatic cancer have a mutation in an inherited cancer gene.  In a study of over 300 patients with pancreatic cancer (and with one or two family members with pancreatic cancer), 12% were found to have a mutation in 1 of 11 genes, most commonly BRCA2 and ATM.1 In a subsequently published study of 274 patients with pancreatic cancer (unselected for family history), almost 9% had a mutation in an inherited cancer gene.2 Through another large study of over 3000 pancreatic cancer patients, mutations in 6 genes associated with pancreatic cancer were found in 5.5% of these patients (including 7.9% and 5.2% of patients with and without a family history of pancreatic cancer).3 Most recently, ~10% of almost 300 unselected pancreatic cancer patients were found to have a mutation in an inherited cancer gene, most of which were genes known to be associated with pancreatic cancer.4 Many of these individuals did not meet current clinical criteria to warrant testing. Taken together, these findings highlight the importance of broadly considering testing for inherited cancer genes among individuals with pancreatic cancer, which is particularly important given the advances in targeted therapeutics.

1Chaffee KG, et al. Genet Med. 2018 Jan. PMID:  28726808.
2Young EL, et al. BMC Cancer. 2018 Jun 27. PMID: 29945567.
3Hu C, et al. JAMA. 2018 Jun 19. PMID:29922827.
4Brand R, et al, Cancer.2018 Aug 1. PMID: 30067863.




ICARE Newsletter Summer 2018

Community Spotlight

I was aware from a very young age that breast cancer was part of our family. I knew that my great-grandmother (whom I never met) had breast cancer and my grandmother was diagnosed in her 50’s. While I didn’t grow up being afraid of the disease, I was far more aware of it than were any of my friends. My mom was diagnosed with a uterine sarcoma in her mid-40’s and breast cancer at age 48, and again at age 54. She underwent a few grueling surgeries, but was spared chemotherapy and radiation. She also had her ovaries removed prophylactically, years before it was considered a “viable” option. My grandmother died in her 70’s from complications of ovarian cancer, and my mom lived until she was 81 when she succumbed to Alzheimer’s disease.

When I learned about genetic testing for the BRCA genes in spring of 2000, my mother and I had testing through Vanderbilt’s genetic counseling program and learned we were both BRCA2 positive; my two sisters tested negative. After much research—I met with numerous oncologists, surgeons, and plastic surgeons, and learned everything I could about possible insurance ramifications to any decisions I might make—I decided to have a complete hysterectomy and a prophylactic bilateral mastectomy with reconstruction.

During this time, I turned to FORCE (Facing Our Risk of Cancer Empowered) for much of my research and critical emotional support. My family was extremely supportive; my husband was “all in” despite having no prior experience with cancer. I felt lucky to have three healthy children (ages 3, 6, and 9 at the time) and was ready to undergo these surgeries to lower my cancer risks. The surgeries didn’t scare me because I had watched my mother successfully undergo tough surgeries. Primarily, I was afraid of the unknown.

It’s been 17 years since then, and I have no regrets. I’m eternally grateful for the research dedicated to hereditary cancers, the familial support I received, and the peace of mind my surgeries brought. I participate in ICARE and other related activities in hopes that continued research will positively impact all of us with hereditary cancers, and especially my three children who are now young adults. From my mom, I gleaned two thoughts I hope I’ve passed on to my children: live every day to the fullest; and knowledge is power. Because of my mother’s legacy and willingness to tackle this very tough issue, my kids are armed with information they can use as they grapple with difficult decisions in the years ahead.

  ―ICARE Participant, Patricia Blumenthal




ICARE Newsletter Summer 2018

Another PARP-Inhibitor Trial Among BRCA Carriers with Advanced Breast Cancer

In a Phase 3 clinical trial among BRCA carriers with advanced breast cancer, an oral PARP Inhibitor (talazoparib) was compared to standard chemotherapy.  Among those who received the PARP inhibitor, risk of disease progression or death was 46% lower, and the response rate was double. Furthermore, the side effect profile, quality-of-life measures, and breast cancer symptoms were more favorable in the PARP inhibitor group. These findings indicate that talazoparib among this group of patients results in longer progression-free survival than standard chemotherapy, with better patient-reported outcomes.

Litton JK, et al.. N Engl J Med. 2018 Aug 15. PMID: 30110579.




ICARE Newsletter Summer 2018

Ask the Expert

The following question was addressed by Ronald D. Alvarez, MD, MBA who is Professor, Chairman, and Clinical Service Chief of the Department of Obstetrics and Gynecology at Vanderbilt University Medical Center in Nashville, Tennessee. Dr. Alvarez has been the recipient of several National Cancer Institute (NCI) and other industry funded grants in support of his research in gene therapeutics for ovarian cancer. He has served on the editorial board of Gynecologic Oncology and currently serves as Director of the Gynecologic Oncology Division for the American Board of Obstetrics and Gynecology.

Q. After an ovarian cancer diagnosis, should women with a BRCA mutation consider a risk-reducing mastectomy?

A. Among women with ovarian cancer who are found to have a BRCA1 or BRCA2 mutation, there is a lack of clear guidance as to when and in whom to consider risk-reducing mastectomy. In a study based on BRCA carriers (which included ICARE participants), 4% of these women developed breast cancer ten years following the ovarian cancer diagnosis. However, benefits of mastectomy (as well as breast MRI for early breast cancer detection) were primarily seen among women who had survived 10 years following their ovarian cancer diagnosis (without any disease recurrence) or had early stage (stage I or II) ovarian cancer. Consequently, risk-reducing mastectomy or breast MRI may be considered among BRCA carriers with ovarian cancer without a personal history of breast cancer and no evidence for recurrence for 10 years, as well as among those with early stage disease.

McGee J, et al. Gynecol Oncol. 2017 May. PMID: 28314588.




ICARE Newsletter Winter 2018

Community Spotlight

A cancer diagnosis is a life-changing event for every patient and their extended family. However, how we respond to this diagnosis are as individual as our very existence as evidenced by our looks and personalities. Following my diagnosis of stage 4 prostate cancer in 2014 at age 54 which had spread to my bones, I was initially crushed, especially when I found out that I was in the very small percentage for whom there really was no cure. I then did what I always do, just like I did when my son with Down’s syndrome was born – I tried to gather all the knowledge to make the best decisions to move forward. As with my son, who is now a 22 year old with a loving personality and working, my goal is to pursue the best outcome possible.

With a background of many immediate and extended family members with cancer, the decision to do genetic testing was easy, through which I found out that I was positive for the BRCA2 genetic mutation, which was not very surprising. Since all four of my children are now young adults between 21-33 years old, we had a great discussion about future testing and what this means. To my knowledge, none of them have completed testing yet, but they have all been like their old man…happy to have the knowledge to help them make good decisions on their own future preventive care. I am also personally glad they are armed with good information.

As for my own future, so far I am exceeding expectations. The first treatment was expected to last 18-24 months, but mine lasted 40 months! Now moving into what is called “advanced prostate cancer” I continue to be happy that my quality of life is still good. I also continue to rest in my faith and trust God for whatever future that remains.

  ―Ben Williams, Colonel, US Army, Retired




ICARE Newsletter Winter 2018

Advances in the Understanding of Inherited Prostate Cancer

Findings through a recent study reported that inherited cancer gene mutations were present in 8.2% of those with advanced or metastatic prostate cancer, which provides additional support to include this group of men in broader testing, particularly as targeted treatments based on inherited gene mutations becomes increasingly available.1 Another recent study suggested that those with a stronger family history of prostate cancer were more likely to present with more advanced prostate cancer, suggesting that familial or hereditary prostate cancer may be associated with a more aggressive disease.2 In view of these and other recent advances in the understanding about inherited prostate cancers, a group of experts convened to develop a consensus statement to guide the identification, management, and testing of men at risk for inherited prostate cancer.3 Overall, there was broad agreement for discussion of prostate cancer screening among BRCA2 carriers. Furthermore, there was moderate consensus that BRCA2 should be factored into management decisions from an early stage in the patient’s treatment, with stronger consensus that this is very important to consider among those with advanced or metastatic disease. Genetic testing for all men with metastatic castration-resistant prostate cancer regardless of family history was also considered to be important to inform prognosis and targeted therapy, particularly for the BRCA1 and BRCA2 genes, and possibly for the ATM gene.

1Thalgott et al. World J Urol. 2017 Nov 21. PMID:29164326.
2Giri et al. JCO Precision Oncology 2017 May 4;1, 1-17.
3Giri et al. J Clin Oncol. 2017 Dec 13. PMID:29236593.




ICARE Newsletter Winter 2018

Updates to NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian Guidelines

(Version 1.2018, posted Oct. 3, 2017)

  • Metastatic prostate cancer was added as an indication for evaluation and testing for the BRCA1 and BRCA2 genes
  • Among BRCA1, BRCA2, TP53 and PTEN carriers, women between ages 25-29 may consider having an annual mammogram with consideration of tomosynthesis if a breast MRI is not available.
  • Among female BRCA2 carriers, language regarding age of risk-reducing salpingo-oophorectomy (surgical removal of one or both ovaries and fallopian tubes) was updated to indicate that it may be delayed to age 40-45
  • The table for other inherited breast and ovarian cancer genes was updated per the recent advances.

For the complete updated versions of the NCCN Guidelines, please visit NCCN.org




ICARE Newsletter Winter 2018

Refining Risks and Outcomes of Breast Cancer in BRCA Carriers

In an effort to further study breast cancer risks among BRCA carriers, a recently published study compared breast cancer risks among those with and without a close family member (first-degree relative) with breast cancer.1 Findings showed that risk for breast cancer by age 80 was 60.8% in BRCA1 carriers and 63.1% among BRCA2 carriers, with similar risk levels among those with and without breast cancer in a close relative. These findings suggest that breast cancer risks remain high among BRCA carriers, regardless of whether a woman has a close relative with breast cancer, thus cancer risk management should be the same for these women.

In considering outcomes of breast cancer, prior studies have not yet provided evidence to draw a definitive conclusion about whether BRCA carrier patients with breast cancer do better, worse, or no different, compared to patients with ‘sporadic’ (or non-hereditary) breast cancer. A new study was recently published to answer this question.2 In this study, breast cancer patients diagnosed at or below age 40 (within 12 months of their diagnosis) were followed over time to compare the outcome between those with and without a BRCA mutation. Findings from this study showed that BRCA carriers had similar overall survival to non-carriers. Furthermore, the study showed that those with a BRCA mutation and triple-negative breast cancer may have a better outcome (as defined by survival) in the first few years after diagnosis.

1Metcalfe et al. Clin Genet. 2017 Dec 5. PMID:29206279.
2Copson et al. Lancet Oncol. 2018 Jan 11. PMID 29337092.




ICARE Newsletter Winter 2018

FDA Approval of PARP Inhibitor (Lynparza) for Treatment of Advanced Breast Cancer

On January 12, 2018, the FDA approved the first PARP Inhibitor (Lynparza) for treatment in patients with advanced breast cancer due to inherited BRCA mutations.1 This drug is already approved for certain BRCA carriers for advanced ovarian cancer. PARP inhibitors were originally developed to target the specific pathway through which cancer develops among those with a BRCA mutation. This latest approval demonstrates that developing drugs to target the underlying genetic cause of cancer can be used across cancer types. The approval of this drug was based on a recently published trial which showed that the drug delayed disease progression, which may help preserve quality of life by delaying the use of chemotherapy.2 It remains to be determined whether further improvements in treatment with this drug can be achieved through using it in combination with other drugs.

1https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm592347.htm
2Robson et al. N Engl J Med. 2017 Aug 10;377(6):523-533. PMID: 28578601.




ICARE Newsletter Winter 2018

Ask the Expert

The following question was addressed by Dr. Ingrid Meszoely is a breast surgeon and Clinical Director of the Vanderbilt Breast Center at One Hundred Oaks. She leads a high-risk clinic, through which she and her team of nurse practitioners manage patients with inherited breast cancer predisposition. Her research interests include both clinical and translational breast cancer-related research.

Q. Is it reasonable to consider hormonal replacement therapy (HRT) in BRCA carriers without breast cancer, after a prophylactic oophorectomy (surgical removal of one or both ovaries)?

A. There have been prior concerns that HRT may raise the risk of breast cancer among BRCA carriers, yet data from multiple studies which have evaluated this question have been reassuring. Specifically, three studies (observational and retrospective studies) have been completed in BRCA mutation carriers without a history of breast cancer, in which HRT did not raise the subsequent risk of breast cancer, nor did it appear to reduce the protective effect of oophorectomy on breast cancer risk.1,2,3 While it would be ideal to confirm these findings through a randomized control trial, data are currently reassuring that HRT is an option that may be considered among BRCA carriers, particularly those with severe menopausal symptoms or other issues that compromise their quality of life. In fact, a recent study on a group of 178 premenopausal women at high risk for ovarian cancer reported that about one third (n=57) opted for risk-reducing salpingo-oophorectomy (RRSO; removal of both ovaries and fallopian tubes).4 Of those with RRSO, 27 used HRT after surgery and 30 did not. HRT users had less menopausal side effects (i.e., endocrine symptoms, sexual symptoms) compared to those with did not use HRT, suggesting the potential benefits of this treatment in the first year following RRSO.

1Eisen, A. et al. J Natl Cancer Inst. 2008 Oct 1;100(19), 1361-7. PMID:18812548.
2Rebbeck, T.R., et al. J Clin Oncol. 2005 Nov 1;23(31), 7804-10. PMID:16219936.
3Kotsopoulos et al. Breast Cancer Res Treat. 2016 Jan;155(2):365-73. PMID:26780555.
4Vermeulen et al. Eur J Cancer. 2017 Oct;84:159-167. PMID: 28818705.




ICARE Newsletter Winter 2018

Study Suggests Inherited Cancer Genes Are Important in Pancreatic Cancer

In a recent study which included over 800 patients with pancreatic ductal cancer, inherited cancer gene mutations were found in a much higher proportion than expected. Almost 5% of these patients had mutations identified in inherited cancer genes, the majority of which were in genes thought to be associated with pancreatic cancer (including BRCA2, ATM, BRCA1, PALB2, MLH1, CDKN2A, and TP53).  Those that had mutations identified tended to be younger on average, however most did not have a family history of cancer that would suggest the presence of inherited mutations. These findings demonstrate that a meaningful number of patients with inherited risk for pancreatic cancer will be missed if relying on only family history. With the development of drugs to target cancers which develop among those with inherited disease, this study shows that relying too heavily on family history may lead to missing patients who would otherwise be eligible for these targeted treatments.

Shindo et al. J Clin Oncol. 2017 Oct 20;35(30):3382-3390. PMID: 28767289.




ICARE Newsletter Summer 2017

Ask the Expert

The following question was addressed by Dr. Steven Narod who is a Tier I Canada Research Chair in Breast Cancer and a senior scientist at the Women’s College Research Institute in Toronto, Canada. Dr. Narod is a world-leader in the field of breast and ovarian cancer genetics.

Q. In women with a BRCA mutation and ovarian cancer, who might benefit the most from MRI screening or mastectomy?

A. Although risk-reducing mastectomy (RRM) and MRI screening are routinely offered to unaffected BRCA carriers, there are limited studies to guide whether those with a history of ovarian cancer would also benefit from RRM or MRI screening. We recently studied this question among 509 BRCA carriers with ovarian cancer through our registry database.1 We found that twenty (3.9%) patients developed breast cancer within the 10 years following their ovarian cancer diagnosis. Through simulation results, we were able to show limited benefit from MRI screening or RRM among most patients. However, our data suggests that women who had already survived 10 years or more following ovarian cancer or those with early stage ovarian cancer (stage I or II) could benefit from MRI or RRM. Based on these findings, we suggest that BRCA carriers with an ovarian cancer diagnosis and no prior history of breast cancer may benefit from MRI or RRM when they are 10 years out from their ovarian cancer diagnosis without a recurrence, or if they were diagnosed with early stage ovarian cancer.




ICARE Newsletter Summer 2017

Breast and Ovarian Cancer Risks Among BRCA Carriers Followed Over Time

Findings from an international study of over 6000 women with a BRCA1 mutation and almost 4000 women with a BRCA2 mutation followed for an average of 5 years were recently published.1 Results showed the risk of breast cancer by age 80 was ~70% for both BRCA1 and BRCA2 carriers. Rates of breast cancer increased until age 30-40 in BRCA1 carriers and 40-50 in BRCA2 carriers, after which they remained constant over time to age 80. Risk of ovarian cancer by age 80 was 44% among BRCA1 carriers and 17% among BRCA2 carriers. Among women with a prior breast cancer diagnosis, the risk of developing another new breast cancer in the other breast (called “contralateral breast cancer”) after 20 years was 40% for BRCA1 carriers and 26% for BRCA2 carriers. Overall, the risk of breast cancer was higher in individuals who had more relatives with breast cancer. Consistent with findings published by Rebbeck et al. in 2015 in JAMA, there were certain locations of the gene mutation that presented a higher risk for breast cancer2 – specifically, risks of breast cancer were higher for: 1) BRCA1 if the mutation was outside the region between c.2282-c.4071 and 2) BRCA2 if the mutation was outside the region between c.2831-c.6401. Ultimately, findings from the current study provide information to better predict cancer risks based on family history and mutation location, which may contribute to developing and improving personalized cancer risk management for women with mutations in these genes.

1Kuchenbaecker et al.  JAMA. 2017 Jun 20;317(23):2402-2416. PMID: 28632866.
2Rebbeck et al.  JAMA 2015 Apr 7;313(13):1347-61. PMID: 25849179.




ICARE Newsletter Summer 2017

Community Spotlight

After a long rainy summer filled with doctor visits, I was finally diagnosed with triple-negative inflammatory breast cancer (TN IBC) at the age of 49. I completed treatment in June 2008 and was grateful to have a new phase to my vocabulary – NED, ‘no evidence of disease’. Since there was no cancer history in my family tree, genetic testing was not offered to me. Fast forward to 2013, with a stronger knowledge base of BRCA gene testing, my medical team suggested I be tested and I agreed. My test results revealed that I carried a BRCA1 mutation, which meant that my children could have the gene as well. I strongly feel that any tool that can be of help to my family to be educated is important, as well as helping medical advancement. This testing could let my children and grandchildren know if they are at risk for breast and ovarian cancers. My three daughters subsequently had testing and my oldest daughter, Natalie, was also found to have this mutation. As Natalie has so eloquently stated after finding out, “I’m glad I’m armed with this knowledge so I can make informed decisions.” [https://www.theibcnetwork.org/moms-daughters/].

After my diagnosis of IBC, I was shocked at how little information was available regarding this type of breast cancer, and even more shocked at the lack of research and education considering it was first written about in the 1800’s. I formed the IBC Network Foundation, to encourage education and fund research for this orphaned form of breast cancer. I am pleased that we have managed to put almost 1 million dollars to research in five years. Our impact is now global, as we also have a sister charity in the UK funding research.

Vanderbilt is a leading cancer center, but I became familiar with some interest in TN IBC over a chance meeting with some researchers at a conference. I was pleased to see their passion and therefore saw the need for funding. Our foundation has committed to funding TN research at Vanderbilt.

Upon learning about the Inherited Cancer Registry (ICARE) based at Vanderbilt, I was excited to join to contribute to the research mission, as well as being given the opportunity to receive regular research and clinical updates. As much as it might seem frightening to some to join a registry like this, I am grateful for the opportunity to help pay it forward by supporting inherited cancer studies in the hopes we can all live well and have long healthy lives. 

Terry Arnold, ICARE Participant




ICARE Newsletter Summer 2017

New Results of a PARP Inhibitor Study Among BRCA Carriers with Metastatic Breast Cancer

Over the last decade, a new class of drugs called “PARP Inhibitors” has been evaluated as a form of targeted treatment among BRCA carriers. Results were recently reported from a Phase 3 clinical trial among BRCA carriers with HER2-negative metastatic breast cancer who received two or less prior chemotherapy regimens for their metastatic disease. Study participants received either the PARP inhibitor (olaparib) or standard treatment, and the primary outcome measured was progression-free survival (i.e. the length of time during and after the treatment where the cancer does not get worse). Of the 302 women who participated in this study, progression-free survival was ~3 months longer among those who received olaparib compared to standard treatment. Side effects from treatment and treatment discontinuation were also lower in the olaparib group.  Furthermore, progression of disease or death was 42% lower among those given olaparib. Although no PARP inhibitor is yet FDA-approved for breast cancer, these results demonstrate the type of evidence needed to move a drug from the clinical trials setting to an FDA-approved treatment and highlight the expansion of personalized treatments among BRCA carriers.

Robson et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017 Jun 4. PMID: 28578601.




ICARE Newsletter Summer 2017

What Are the Benefits of Adding a Mammogram to MRI for Breast Cancer Screening Among Women with BRCA Mutations?

Recently, researchers evaluated the benefit of adding a mammogram to MRI for breast cancer screening among ~2000 women with a BRCA1 or BRCA2 mutation. Results indicated that the addition of mammography to MRI did not substantially raise the chance of detecting breast cancer in the overall group. However, one-third of breast cancer cases diagnosed among women age 40 and below with a BRCA2 mutation were detected by mammograms alone. Consequently, this study suggests a limited benefit from mammography over and above MRI among BRCA1 carriers, but a potential benefit among BRCA2 carriers, particularly those at or below age 40. This type of information may eventually help tailor screening approaches among BRCA carriers.

Phi et al. Br J Cancer. 2016 Mar 15;114(6):631-7. PMID: 26908327.




ICARE Newsletter Summer 2017

Breast and Ovarian Cancer Associations for Genes Tested Through Multi-Gene Panels

As testing for multiple genes at the same time (“multi-gene panel testing”) has become increasingly available with tremendous advances in genetic testing technology, it has become critical to evaluate and refine cancer associations and levels of risk for many of these genes now tested. Through a commercial laboratory database of almost 100,000 results of multi-gene panel testing, associations between mutations in specific genes with breast and ovarian cancers were evaluated. Findings indicated that 8 genes were associated with breast cancer and 11 genes were associated with ovarian cancer. Most had previously been confirmed in association with breast cancer, including ATM, BRCA1, BRCA2, CHEK2, PALB2, PTEN, and TP53. An additional newer gene, BARD1, was also found to be associated with breast cancer in this dataset, but remains a gene for which data continues to emerge to help determine whether a true association with breast cancer exists.  Similarly, for ovarian cancer, most genes identified to have an association were consistent with data from prior studies, including BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, STK11, RAD51C, and RAD51D. Additional genes that were shown to have an association with ovarian cancer in this dataset included ATM and NBN, however additional research is needed to determine if an association with ovarian cancer truly exists. Ultimately, there remains a great need to continue to evaluate cancer risks for inherited genes for which we have limited information about level of risk and types of associated cancer.

Kurian et al. JCO Precision Oncology. 2017 :1, 1-12




ICARE Newsletter Winter 2017

Newly Approved PARP-Inhibitor (Rucaparib) to Treat BRCA Carriers with Ovarian Cancer

The FDA just approved another PARP inhibitor, rucaparib, for BRCA carriers with ovarian cancer who have already been treated with two or more chemotherapies. Among those with BRCA-mutant ovarian cancers, 54% had a partial or complete response to the drug with a median duration response of 9.2 months. The agency also approved a companion diagnostic test through Foundation Medicine, FoundationFocusTM which may be used in tandem. FoundationFocus CDxBRCA is a tissue-based test that detects tumor BRCA1 and BRCA2 mutations (germline and/or somatic) in ovarian cancer.

What remains interesting is that despite the availability of the companion diagnostic test, FoundationFocus, this test may not be required to determine eligibility for the drug – in fact, those determined to have a germline mutation in BRCA1/2 through any commercial laboratory may be eligible to receive this drug.




ICARE Newsletter Winter 2017

New Study Suggesting BRCA1/2 and ATM Are Associated with Aggressive Prostate Cancer

Among 799 patients with prostate cancer, the rate of BRCA1/2 mutations was much higher among those who passed away of prostate cancer (6.07%) compared to those with low risk disease (1.44%).1 Among the group that died of prostate cancer, those with BRCA1/2 or ATM mutations passed away at an earlier age and had a shorter survival time compared to date of diagnosis. These findings suggest that prostate cancer patients with inherited mutations in BRCA1/2 and ATM have a poorer prognosis, with a higher risk of dying at an earlier age. These results are consistent with results of prior efforts, and highlight the importance of genetic testing among these patients to inform decisions regarding prostate cancer screening and treatment.

1Na R, et al. Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death. Eur Urol. 2016 Dec 9. [Epub ahead of print]; PMID: 27989354.




ICARE Newsletter Winter 2017

Ask the Expert

The following question was addressed by Dr. Steven Narod who is a Tier I Canada Research Chair in Breast Cancer and a senior scientist at the Women’s College Research Institute in Toronto, Canada. Dr. Narod is a world-leader in the field of breast and ovarian cancer genetics.

Q. Does salpingo-oophorectomy reduce the risk of breast cancer in those with BRCA mutations

A. Among women in the general population, risk-reducing salpingo-oophorectomy (RRSO) (i.e. removal of the ovaries and fallopian tubes) is recommended to reduce the risk of ovarian and fallopian tube cancer. The removal of the ovaries may reduce the risk of breast cancer as well. In the general population removal of the ovaries before menopause cuts the risk of breast cancer by 30% or more. Similarly, early studies in BRCAcarriers in the United States (US) suggested that removal of the ovaries also cuts their breast cancer risk by half or more, especially when done at an early age. However, a recent Dutch study did not observe a reduced risk of breast cancer after RRSO in BRCA1 carriers.1 The authors of this Dutch study suggest that previous findings may have been due to the design of the studies and how the data was analyzed and casts doubt on the earlier studies. The original US-based study teams subsequently re-analyzed their data but still concluded that RRSO reduced breast cancer risk among BRCA1 and BRCA2 carriers.2

Subsequently, our group led an international study with data from many centers (including ICARE participants) and included almost 4000 BRCA carriers. These women were followed for up to ten years for new cases of breast cancer. The study showed that RRSO reduced the risk of breast cancer risk in BRCA2 carriers, but did not reduce breast cancer risk among BRCA1 carriers.3

Taken together, data suggest there is a benefit of RRSO to lower breast cancer risk among BRCA2 carriers, but not BRCA1 carriers. However, given the strong protective effect of oophorectomy on ovarian cancer risk and on all-cause mortality we recommend an oophorectomy for BRCA1 carriers at age 35 and for BRCA2 carriers at age 40.4

1Heemskerk-Gerritsen BA, et al. J Natl Cancer Inst. 2015 Mar 18. PMID: 25788320.
2Chai X, et al. J Natl Cancer Inst. 2015 Aug 11. PMID: 26264690.
3Kotsopoulos J, et al. J Natl Cancer Inst. 2016 Sep 6. PMID: 27601060.
4Finch AP, et al. J Clin Oncol. 2014 May 20.PMID: 24567435 




ICARE Newsletter Winter 2017

How Does Having a Mother with Breast Cancer and a BRCA Mutation Affect Adolescent Girls?

A recent study compared psychosocial adjustment and risk perception among 11 to 19 year old daughters of women with breast cancer, comparing those with a BRCA mutation versus those without.1 The overall findings from the study were reassuring, suggesting that adolescent girls from BRCA-positive families had higher self-esteem and similar psychosocial adjustment compared to their peers without a family history of breast cancer. On the other hand, not surprisingly, girls from BRCA-positive families experienced more distress related to breast cancer and being susceptible to the disease compared to girls without a family history of breast cancer. Overall, study findings suggest there remains a need to better understand how being from a BRCA-positive family may impact adolescent girls, in order to develop strategies which address any psychosocial concerns that may be demonstrated.

1Bradbury AR, et ak. Psychosocial Adjustment and Perceived Risk Among Adolescent Girls From Families With BRCA1/2 or Breast Cancer History. J Clin Oncol. 2016 Oct 1;34(28):3409-16. PubMed PMID: 27551110.




ICARE Newsletter Summer 2016

What Are the Endometrial Cancer Risks Among BRCA Carriers?

Although BRCA mutations confer increased risk for ovarian, fallopian tube, and primary peritoneal cancer, there have been limited and conflicting risks reported for endometrial cancer. Consequently, current practice guidelines only recommend the removal of the fallopian tubes and ovaries as a risk-reducing option for BRCA carriers.1 Specifically, through a prospective study of 4500 women with a BRCA mutation, there were 17 women identified with endometrial cancers (13 in BRCA1 and 4 in BRCA2) with an average follow-up time of 5.7 years.2 This suggested an overall endometrial cancer risk of 2-fold; although risks were higher (~4-fold) in those who received tamoxifen. The incidence of endometrial cancer was 2% at 10-years among those treated with tamoxifen. A subsequent study by the same group suggested the increased endometrial cancer risks among those with a history of tamoxifen use was associated with progesterone-only hormone replacement therapy, which warrants further study.3 These findings suggest that tamoxifen contributed substantially to the endometrial cancers seen among BRCA1 mutation carriers, although the actual risk is still fairly small. Consequently, in those considering tamoxifen, it may be important to discuss hysterectomy at the time of risk-reducing salpingo-oophorectomy (RRSO).

More recently, a prospective study of almost 1,100 BRCA carriers who had previously undergone removal of their tubes and ovaries, demonstrated an increased risk in BRCA1 carriers for a type of endometrial cancer called serous/serous-like. In this study, 8 women with endometrial cancer (of which 5 were serous/serous-like) were identified over an average follow-up time of 5.1 years.4 This suggested an overall elevation in endometrial cancer risk of almost 2-fold. The association of serous/serous-like endometrial cancer is particularly relevant as it only accounts for approximately 10% of endometrial cancer cases in the general population and is typically associated with aggressive disease and poor prognosis. As eloquently reviewed in the Leath et al editorial for this article,5 the risk of serous endometrial cancer among BRCA1 carriers may warrant a discussion of the potential risks and benefits of hysterectomy at the time of RRSO as well as a discussion about the limitations of our current knowledge in order for patients to make an individualized decision. In fact, a recent report of cancer risks among relatives of over 1000 BRCA mutation carriers detected no increased risk of endometrial cancer,6 highlighting the limited (if any) elevation of endometrial cancer risk. Taken together, these findings emphasize the need for further studies to refine risks and determine the need for hysterectomy both at time of RRSO as well as the role (if any) of risk-reducing hysterectomy among those who have already had an RRSO (as the risk of a second surgery may be greater than the risk of endometrial cancer).

1National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Genetic Familial High-Risk Assessment: Breast and Ovarian. Version 1.2016. Retrieved from: www.nccn.org.
2Segev Y, et al. Gynecol Oncol. 2013 Jul;130(1):127-31. PMID: 23562522.
3Segev Y, et al. Fam Cancer. 2015 Sep;14(3):383-91. PMID: 25838159.
4Shu CA, et al. JAMA Oncol. 2016 Jun 30. PMID: 27367496.
5Leath CA, et al. JAMA Oncol. 2016 Jun 30. PMID: 27367041.
6Streff H, et al. Oncologist. 2016 Jul;21(7):869-74. PMID: 27306910.




ICARE Newsletter Summer 2016

Ask the Expert

The following question was addressed by Dr. Christine Laronga at the Moffitt Cancer Center:

Q. How should bone health be monitored in women with a BRCA mutation after removal of the ovaries (i.e., risk-reducing salpingo-oophorectomy (RRSO))?

A. Women with a BRCA mutation have a substantially high risk to develop ovarian cancer in their lifetime, yet there is currently no reliable screening method to detect ovarian cancer before it spreads beyond the ovaries.  Consequently, RRSO among BRCA carriers is generally recommended around age 35-40, recognizing that childbearing plans are a consideration when deciding on age at which to have this surgery. However, this surgery also leads to early menopause which affects bone health. A recent study looked at women with a BRCA mutation who had undergone RRSO and showed that only 44% of these women had gotten at least one DXA scan (which is a radiological test that measures bone density). Of these women, 32% had normal results, 55.6% had osteopenia (reduced bone density), and 12.1% had osteoporosis. Additionally, 4% of women had a fracture (not related to trauma) after surgery. Low bone density was not related to age, breast cancer history, prior chemotherapy, or hormone receptor blocker treatment, suggesting that this was mainly due to removal of the ovaries. These findings suggest that RRSO in BRCA carriers is a strong risk factor for bone loss – as a result, it may be prudent to offer these women screening for bone health following RRSO to allow for timely intervention. Furthermore, although there is a lack of data regarding the best interval for bone density screening among carriers following RRSO, obtaining a baseline DXA and then screening every two years is reasonable to consider in these women.

Garcia C, et al. Gynecol Oncol. 2015 Sep;138(3):723-6. PMID: 26086567.




ICARE Newsletter Summer 2016

Inherited Cancer Genes and Metastatic Prostate Cancer

Several prior studies have suggested that men with a BRCA mutation (primarily BRCA2) tend to develop an aggressive form of prostate cancer that is more likely to metastasize. These findings were recently extended through a new study published in the New England Journal of Medicine.1 In this study, almost 700 men with metastatic prostate cancer, unselected for strong family history or young age, were tested for mutations in 20 inherited cancer risk genes involved in repairing DNA damage.  Germline (inherited) mutations were identified in 82 men (11.8%), of which the most frequently mutated gene was BRCA2 (5.3%). Mutation frequency among those with metastatic prostate cancer was substantially higher than those with localized disease where only 4.6% were identified to have a mutation (p<0.001). Notably, unpublished findings presented during the 2016 American Urological Association Meeting suggested that among men with prostate cancer, BRCA mutations were significantly more common among African Americans (7.2%) compared to Caucasians (2.1%), with borderline significant results (p=0.052) of a shorter time to metastasis among African Americans. 2 Taken together, the much higher than expected frequency of inherited mutations identified among men with metastatic prostate cancer regardless of age or family history (even more so among those who are African American) in conjunction with potential relevance to targeted treatments suggest that it may be appropriate to offer genetic testing for inherited cancer genes involved in DNA repair to all men with metastatic prostate cancer.

1Pritchard CC, et al. N Engl J Med. 2016 Jul 6. PMID: 27433846.
2Petrovics G., et al.  Higher Frequency of Germline BRCA1 and BRCA2 Mutations in African American Prostate Cancer.  Presented at the 2016 American Urological Association as Abstract #MP39-18.




ICARE Newsletter Winter 2016

How Much Does Age at First Breast Cancer Affect the Risk of Contralateral Breast Cancer Risk in BRCA Carriers?

A recently published study of Dutch patients (including 200 BRCA1 carriers, 71 BRCA2 carriers, and 6023 non-carriers) showed that the contralateral breast cancer (breast cancer in the opposite breast) risks at 10 years was 21.1% for BRCA1, 10.8% for BRCA2, and 5.1% for non-carriers. Among BRCA mutation carriers, it was important to take age at diagnosis of the first breast cancer into account to refine the 10-year risk of a second breast cancer diagnosis as follows: for those diagnosed at age 40 or younger, risks were 25.5% for BRCA1 and 17.2% for BRCA2; for those diagnosed between 41-49 years, risks were 15.6% for BRCA1 and 7.2% for BRCA2.  These findings show that it is important to provide age-specific risk estimates to BRCA mutation carriers as part of the counseling process in order for patients to make informed decisions about their cancer risk management.

 van den Broek AJ, et al. J Clin Oncol. 2015 Dec 23.PMID: 26700119.




ICARE Newsletter Winter 2016

Ask the Expert

The following question was addressed by Dr. Christine Laronga at the Moffitt Cancer Center:

Q. As a BRCA carrier, is it reasonable for me to consider nipple-sparing mastectomy (compared to total mastectomy) to reduce my future risks of breast cancer?

A. One  strategy to manage the high (60-70%) lifetime breast cancer risk among women with a BRCA mutation is risk-reducing bilateral total mastectomy (not subcutaneous mastectomy where a rim of breast tissue is intentionally left on the underside of the breast skin to afford a more natural feel to the reconstructed breast). This procedure reduces the risk of developing breast cancer by 90% or more.  In the past, the entire breast with the overlying nipple and areolar disk was removed when performing this surgery, but more recently there has been an increase interest in preserving the nipple (“nipple-sparing” mastectomy). For many women, the nipple is what defines the breast as a breast.  Prior studies have shown that some patients have psychosocial benefit when the nipple-areolar complex is spared, and for some, the inability to preserve the nipple may be a barrier to even consider mastectomy.

A recent study measured the amount of breast tissue that remains when the nipple is spared with a standard retroareolar margin of 5 mm, and found that this only encompasses 1.3% less of the total at-risk breast tissue among women with BRCA mutations.1 Additionally, two recent studies showed that among BRCA carriers with nipple-sparing mastectomy, fewer than 2% developed subsequent cancers and none were in the nipple-areolar complex.2,3  Furthermore, there was a low rate of complications and no evidence that safety in the cancer setting was compromised.  Although there remains a need for studies with a longer follow-up time, currently available information suggests that it is reasonable for women with a BRCA mutation to consider nipple-sparing mastectomy for both breast cancer risk-reduction and treatment.

From a surgical standpoint, there are different ways of reducing the amount of remaining breast tissue when performing this surgery.  When choosing this surgery, it is important to go to a surgeon who is experienced in this procedure in order to maximize risk reduction and minimize complication rates. 

1Baltzer HL et al. Ann Surg Oncol. 2014 May;21(5):1583-8. PMID: 24526546
2Yao K et al. Ann Surg Oncol. 2015 Feb;22(2):370-6. PMID: 25023546
3Manning AT et al. Br J Surg. 2015 Oct;102(11):1354-9. PMID: 26313374




ICARE Newsletter Winter 2016

Potential Use of PARP-Inhibitors Among Men with Prostate Cancer Who Carry a Mutation in BRCA or Other DNA-Repair Gene

A recent study published in the New England Journal of Medicine suggests that PARP-Inhibitors may be of potential use in men who are no longer responding to standard treatments and carry either somatic (i.e., tumor) and/or germline (inherited) mutations in DNA-repair genes (i.e., BRCA1/2, ATM, Fanconi Anemia genes and CHEK2).1 Of 49 men with prostate cancer evaluated through the study, 16 (33%) had somatic mutations in DNA-repair genes.  Of these 16 patients, 14 (88%) responded to the PARP-inhibitor drug (Olaparib), including all 7 patients with BRCA2 mutations (3 with germline mutations and the other 4 with somatic mutations only) and 4 of the 5 ATM mutation carriers. These findings further demonstrate the potential importance of PARP-inhibitors among men with DNA-repair gene mutations in their prostate cancers; however, further studies are needed before these drugs can be considered for routine clinical use.

1Mateo J, et al. NEJM. 2015 Oct 29;373(18):1697-708. PMID: 26510020.




ICARE Newsletter Winter 2016

The Importance of Sharing Genetic Test Results with Family Members

Once an individual has had genetic testing for inherited cancer predisposition this information could help their close family members.  For example, when a BRCA mutation or a mutation in another inherited cancer gene is found, it is important for close family members (with or without a diagnosis of cancer) to know so they too can be proactive with cancer risk management and prevention options if they are identified to also have the familial mutation.  It is usually up to the first individual in the family identified with a mutation to share their positive genetic test result with their relatives.  Unfortunately, prior US-based studies suggest low rates of testing among at-risk family members1 the reasons for which are unclear, although higher rates of testing among family members were reported in a study conducted in Spain.2

It is also important for individuals who are the first person in their family to have genetic testing for inherited cancer and receive a negative result to share their results with family members. This may help to prevent unnecessary testing in the family and/or clarify the meaning of their negative result.

Tools exist to help facilitate sharing of positive test results among family members. These tools include creating a ‘family sharing letter’ to briefly describe the mutation that was found, what it means, and where relatives can access more information. 

1Barsevick AM et al. J Fam Psychol. 2008 Apr;22(2):303-12. PMID: 18410217.
2Sanz J et al. Fam Cancer. 2010 Sep;9(3):297-304. PMID: 20091130.




ICARE Newsletter Winter 2016

More Information About the Inherited Component of Pancreatic Cancer

Although pancreatic cancer is one of the cancer types seen among individuals with mutations in inherited cancer genes (including BRCA2 and BRCA1), the proportion of individuals with pancreatic cancer who have an inherited cause has remained uncertain.  To further clarify the role of BRCA1 and BRCA2 (BRCA), over 300 patients with pancreatic cancer were tested for BRCA mutations.1  BRCA mutations were identified in 4.6% of patients, of which almost 80% were in BRCA2 (with the remainder in BRCA1).  Many of the patients identified with BRCA mutations did not have a strong family history of breast and/or ovarian cancer.  Furthermore, individuals of Ashkenazi Jewish ancestry were more likely to have a BRCA mutation compared to all others.

More recently, another study tested 96 patients with pancreatic cancer for 22 inherited cancer genes, of which 14 mutations were identified in 13 patients (13.5%).2 Nine individuals (9.4%) were identified with mutations in established inherited pancreatic cancer genes of varying risks (i.e., BRCA1, BRCA2, PALB2, MSH6, and ATM). These findings suggest that inherited genes may be a contributing factor in a substantial proportion of individuals with pancreatic cancer.  However, more studies are needed to refine the level of pancreatic cancer risk in order to determine who to target for high-risk screening (recognizing that evidence-based screening strategies for the early detection of pancreatic cancer do not currently exist and remain an active area of research).  Finally, identification of inherited pancreatic cancer predisposition may contribute to targeted treatment approaches. 

1Holter S et al. JCO. 2015 May 4. PMID: 25940717.
2Hu C,et al. CEBP. 2015 Oct 19. PMID: 26483394.




ICARE Newsletter Summer 2015

Location and Type of BRCA1/2 Mutation May Impact Breast and Ovarian Cancer Risks

A study of almost 20,000 BRCA1 carriers and 12,000 BRCA2 carriers demonstrated differences in breast and ovarian cancer risks depending on the location and type of mutation. Although all regions are associated with increased risk for breast and ovarian cancers among BRCA1/2 carriers, there were specific regions that were associated with even higher cancer risks. Specifically, within BRCA1, there were three breast cancer cluster regions located at: 1) c.179-c.505; 2) c.4328-c.4945; and 3) c.5261-c.5563. There was also an ovarian cancer cluster region from c.1380-c.4062.  In BRCA2, there were multiple breast cancer cluster regions spanning c.1-c.596, c.772-c.1806 and c.7394-c.8904.  There were also ovarian cancer cluster regions located at: 1) c.3249-c.5681, adjacent to c.5946delT (i.e., 6174delT) and 2) c6645-c.7471. Furthermore, nonsense mutations (point mutations resulting in a shorter and unfinished protein product) were associated with earlier age of breast cancer diagnosis and differential breast or ovarian cancer risks for both BRCA1 and BRCA2. Overall, this worldwide effort represents the largest study to date to evaluate breast and ovarian cancer risks by location and type of BRCA1/2 mutation. Although results suggest variations in risk, these data require validation prior to BRCA1/2 carriers using the information for cancer prevention decision-making.

Rebbeck TR et al. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA. 2015 Apr 7;313(13):1347-61. PMID: 25849179.




ICARE Newsletter Summer 2015

2015 NCCN Clinical Practice Guideline Update

Breast and Ovarian Management Based on Genetic Test Resultsa

 

Recommend Breast MRIc
(>20% lifetime risk of breast cancerd)

Recommend Risk-reducing salpingo-oophorectomy Discuss Option of Risk-reducing mastectomy
Intervention warranted based on gene and/or risk level ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, STK11, TP53 BRCA1, BRCA2, Lynch syndromee BRCA1, BRCA2, CDH1, PTEN, TP53
Insufficient evidence for
interventionb
BARD1, BRIP1 BARD1, BRIP1, PALB2, RAD51C, RAD51D ATM, BARD1, CHEK2, PALB2, STK11

 

 

 

 

 

 

 

 

 

 

Note: To access full guidelines document, refer to www.nccn.org

aOther genes may be included in mutli-gene testing. cSee NCCN Guidelines for Breast Cancer Screening and Diagnosis.  dMay be modified based on family history or specific gene mutation. eSee NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal.




ICARE Newsletter Summer 2015

Ask the Expert

The following question was addressed to Dr. Steven Narod who is a Tier I Canada Research Chair in Breast Cancer and a senior scientist at Women’s College Research Institute in Toronto, Canada. Dr. Narod is a world-leader in the field of breast and ovarian cancer genetics. Over the course of his career, he has profoundly shaped current knowledge about cancer risks, prevention and screening amongst carriers of BRCA1 and BRCA2 mutations.

Q. As a BRCA mutation carrier, will salpingectomy (removal of the fallopian tubes while keeping the ovaries) lower my risk for developing ovarian cancer?

A. As many ovarian cancers originate in the fallopian tubes, bilateral salpingectomy has been proposed as a consideration among BRCA carriers who are not ready to remove their ovaries.1 Specifically, bilateral salpingectomy has been suggested as an interim procedure to reduce ovarian cancer risk after childbearing is complete, followed by later oophorectomy (removal of the ovaries). At this time there is no data to prove that salpingectomy reduces ovarian cancer risk among BRCA carriers and the benefit is based on theory. In contrast, bilateral salpingo-oophorectomy (i.e., removal of the ovaries and the fallopian tubes) has been shown to reduce the risk of ovarian cancer and of all cause of death dramatically.2 Bilateral salpingectomy has gained interest because it preserves ovarian function, which prevents premature menopause and its associated adverse effects experienced by some women but it cannot yet be assumed to be equivalent to oophorectomy.

1. Walker JL et al. Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer. Cancer. 2015 Mar 27. PMID: 25820366.
2.
Finch AP et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J Clin Oncol. 2014 May 20;32(15):1547-53. PMID: 24567435.




ICARE Newsletter Winter 2015

Highlights of the 2014 National Comprehensive Cancer Network (NCCN) Update

Genetic/Familial High-Risk Assessment: Breast and Ovarian Guidelines

  • For breast cancer screening in BRCA carriers, yearly MRI is recommended starting at age 25; mammograms may be considered in instances where MRI is unavailable or individualized based on earliest age of onset in the family. From age 30-75, annual mammogram and breast MRI is recommended.  Above age 75, management should be considered on an individual basis.
  • In male BRCA carriers, prostate cancer screening through annual PSA and digital rectal exam starting at age 40 was recommended in BRCA2 carriers and a consideration in BRCA1
  • Modifications to TP53 testing and management recommendations
  • Refinement of screening recommendations in PTEN mutation carriers
  • Expansion of the multi-gene testing section including considerations when assessing mutations in less characterized genes and general recommendations.

To access the full guidelines document, refer to www.nccn.org




ICARE Newsletter Winter 2015

PALB2: A Third Important Gene for Inherited Breast Cancer

Following the publication of an important article in the New England Journal of Medicine (NEJM) in August 2014, germline PALB2 gene mutations were confirmed as the third most important gene for inherited breast cancer, following BRCA1 and BRCA2.1 PALB2 stands for “partner and localizer of BRCA2” and is located on chromosome 16. Studies suggest that PALB2 mutations may account for ~2-3% of inherited breast cancer, highlighting its importance as a breast cancer predisposition gene. In those with PALB2 mutations, prior studies suggest: 1) breast cancer risks in women range from two to six-fold; 2) breast cancer risks in men appear to be 8-fold or higher; and 3) risk of pancreatic cancer, although poorly defined, may also be elevated.

While the increased risk of breast cancer in those with a PALB2 mutation has been known for years, genetic testing was not routinely performed because mutations were thought to be rare and cancer risks were unclear. However, declining genetic testing costs due to next-generation sequencing (NGS) technology have revolutionized genetic testing practices through development of multi-gene tests that include BRCA, PALB2, and multiple other genes in one test. As a result, individuals are increasingly being identified with PALB2 mutations. 

The recent NEJM article is the first to broadly address the absolute risk of breast cancer in PALB2 carriers. This international study was based on 154 families with PALB2 mutations, including 311 women and 51 men. In this study, breast cancer risk estimates in those with PALB2 mutations: 1) ranged from 33-58% by age 70 in women depending on family history; and 2) were just over 8-fold in men (although results did not reach statistical significance). Results also suggested that women with a PALB2 mutation were slightly more likely to develop triple negative breast cancer, which is an aggressive type of breast cancer resistant to hormone treatment with a higher chance of recurrence.

“Since the BRCA1 and BRCA2 genes were discovered in the mid-90s, no other genes of similar importance have been found. PALB2 is a potential candidate to be ‘BRCA3’. As mutations in this gene are uncommon, obtaining accurate risk figures is only possible through large international collaborations like this” said lead author of the study, Dr. Marc Tischkowitz from the Department of Medical Genetics at the University of Cambridge, “Now that we have identified this gene, we are in a position to provide genetic counseling and advice. If a woman is found to carry this mutation, we would recommend additional surveillance, such as MRI breast screening.”

Interestingly, PALB2-associated cancers may be sensitive to a new class of drugs known as PARP inhibitors, which are currently under investigation for BRCA-associated cancers. Thus it is possible that these drugs may also work in PALB2-associated cancers.      

There are early suggestions that women with PALB2-associated breast cancer may develop more aggressive disease.2 However, most studies are based on small numbers, thus it remains important to study breast cancer characteristics and outcomes in PALB2 carriers through larger studies. Only through these types of research efforts will we be able to learn more about this important gene and figure out how to better help those with mutations. We are currently recruiting 500 PALB2 mutation carriers to determine breast cancer characteristics and outcomes.

1. Antoniou AC, Casadei S, Heikkinen T, et al. Breast-cancer risk in families with mutations in PALB2. New England Journal of Medicine. Aug 7 2014; 371(6):497-506. 2. Heikkinen T, Karkkainen H, Aaltonen K, et al. The breast cancer susceptibility mutation PALB2 1592delT is associated with an aggressive tumor phenotype. Clinical Cancer Research. May 1 2009; 15(9):3214-3222.




ICARE Newsletter Winter 2015

The First PARP-Inhibitor to Be Approved for Clinical Use in BRCA Carriers

More frequently, cancer drugs are being developed to treat tumors based on their molecular make-up. PARP inhibitors are the first class of drugs specifically developed to treat BRCA-related tumors through targeting the DNA repair pathway. The PARP Inhibitors target this pathway and cause cancer cells to die while healthy cells are spared.

Although PARP inhibitors were developed almost a decade ago, they were only recently approved for clinical use through the U.S. Food and Drug Administration (FDA) after extensive evaluation through clinical trials. Specifically, the PARP inhibitor called Olaparib (Lynparza) was approved for use in BRCA carriers with advanced ovarian cancer treated with three or more prior lines of chemotherapy. 

The effectiveness of this PARP inhibitor, Olaparib, was examined in a study of 137 women with BRCA mutations and advanced ovarian cancer. Results showed that about a third of patients had partial shrinkage or complete disappearance of their ovarian tumor for an average of 8 months. These findings led the FDA to grant accelerated approval of this drug to treat life-threatening disease (because results of the clinical trial showed likely clinical benefit to patients).

Olaparib constitutes the first of a new class of drugs (i.e., PARP inhibitors) for treating ovarian cancer. This drug serves as an example of how the understanding of the underlying molecular mechanisms by which cancer develops can lead to more personalized and effective treatments.

There are many open clinical trials that continue to evaluate PARP inhibitors to determine: 1) when to start treatment with these agents in ovarian cancer patients; 2) whether they work in other BRCA-associated cancers such as breast cancer, pancreatic cancer and prostate cancer (among others); and 3) whether they may also be of benefit to individuals without germline BRCA mutations. Thus it is important to continue evaluating these drugs through clinical trials to determine how they may be best used to treat and perhaps prevent cancer.




ICARE Newsletter Winter 2015

Ask the Expert

The following question was addressed to Dr. Steven Narod who is a Tier I Canada Research Chair in Breast Cancer and a senior scientist at Women’s College Research Institute in Toronto, Canada. Dr. Narod is a world-leader in the field of breast and ovarian cancer genetics. Over the course of his career, he has profoundly shaped current knowledge about cancer risks, prevention and screening amongst carriers of BRCA1 and BRCA2 mutations.

Q. As a BRCA mutation carrier, how much does Tamoxifen reduce my chance of developing contralateral breast cancer?

A. Following an initial breast cancer diagnosis in BRCA mutation carriers, the annual risk for developing contralateral breast cancer (i.e., breast cancer in the other breast) is 3%.1 We have mainly relied on studies evaluating contralateral breast cancer risk reduction with Tamoxifen. These studies have suggested that in women with breast cancer and a BRCA mutation, Tamoxifen reduces the lifetime risk of contralateral breast cancer by ~50%, particularly among those who still have their ovaries.3, 4, 5 Only one study to date with fewer than 20 carriers evaluated Tamoxifen for primary breast cancer prevention and showed risk reduction in BRCA2; however, risk reduction was not confirmed in BRCA1 (but it is important to note that this was a small sample size because there might not have been enough women to find an effect).2 Consequently, Tamoxifen may be considered in BRCA carriers with at risk breast tissue, especially among those who are premenopausal and have their ovaries.

More recently, we evaluated how the duration of Tamoxifen use affected contralateral breast cancer risk.6 We found that the risk of contralateral breast cancer was reduced by about half in those who used Tamoxifen for a short time (less than one year). These results do not imply any changes to the recommended course of Tamoxifen in the context of a breast cancer diagnosis because the primary goal in this situation would be to reduce risk of recurrence. However these results may be relevant for women without a breast cancer diagnosis who are considering Tamoxifen for primary prevention. In these women, consideration of a short course of Tamoxifen may be preferred over the recommended 5-year course, particularly given that many women are reluctant to take the drug because of the fear of side effects.7

Ultimately, we urge women to have a balanced discussion of the potential benefits and harms of Tamoxifen with their healthcare providers to enable them to make an informed decision about using this medication.

1. Metcalfe K, et al. British Journal of Cancer. Apr 26 2011;104(9):1384-1392. 2. King MC, et al. Jama. Nov 14 2001;286(18):2251-2256. 3. Gronwald J, et al. International Journal of Cancer.May 1 2006;118(9):2281-2284. 4. Narod SA, et al. Lancet. Dec 2 2000;356(9245):1876-1881. 5. Phillips KA, et al. J Clin Oncol. Sep 1 2013;31(25):3091-3099. 6. Gronwald J, et al. Breast Cancer Res Treat. Jul 2014;146(2):421-427. 7. Cuzick J, et al. Lancet. Mar 22 2014;383(9922):1041-1048.




ICARE Newsletter Summer 2014

Is Breast Cancer Risk Affected by Timing of Oral Contraceptives in BRCA1 Carriers?

Although oral contraceptives (OC) reduce the risk of ovarian cancer in BRCA carriers,1 it is possible that they may raise breast cancer risk. Thus it is important to understand whether age at OC use is a factor when determining impact on breast cancer risk. To address this question, a recent study (which included data from ICARE participants) of ~5000 women with BRCA1 mutations suggested that use of OC before age 25 increases the risk of early-onset breast cancer, and that the risk becomes higher when used for longer periods of time. Two groups were compared (one with breast cancer and one without) to determine whether age at which OC was used impacted breast cancer risk.  Among BRCA1 carriers, breast cancer risk was higher in those who started OC use before age 20 (Odds Ratio (OR): 1.45; 95% CI 1.20; p=0.0001), and also possibly higher in those between ages 20-25 (OR 1.19; 95% CI 0.99-1.42; p=0.06).

Higher breast cancer risk was limited to breast cancer diagnosed before the age of 40. Overall, the authors reported that the risk of early-onset breast cancer increased by 11% with each additional year of OC use when it was started before the age of 20. However, in those diagnosed with breast cancer at or after the age of 40, there was no increased risk of breast cancer based on OC use. These findings suggest that OC use for the purpose of preventing ovarian cancer should be avoided prior to the age of 25.

1.Kotsopoulos J, et al. Breast Cancer Res Treat. 2014 Feb;143(3):579-86. PMID: 24458845.




ICARE Newsletter Summer 2014

What Are Factors That Modify Cancer Risk in BRCA Carriers?

Since the discovery of the BRCA genes about two decades ago, a number of studies have reported on factors that may modify cancer risks in those who carry gene mutations. Recently, results of previously published studies were collected through a comprehensive literature review to estimate the overall effects of various risk modifiers in BRCA carriers. Results suggested that giving birth for the first time at an earlier age was likely protective against breast cancer risk. Regarding ovarian cancer, breast feeding and tubal ligation reduced risks in BRCA1 carriers, and use of oral contraceptives reduced risks in both BRCA1 and BRCA2 carriers. Interestingly, smoking raised the risk of breast cancer in only BRCA2 mutation carriers. These findings suggest that sufficient information exists on some risk factors, which may be useful when counseling patients about cancer risks or lifestyle factors to modify risks in BRCA carriers.

Friebel TM, et al. J Natl Cancer Inst. 2014 Jun;106(6). PMID: 24824314.




ICARE Newsletter Summer 2014

Early Results to Suggest That PSA Screening May Help to Detect Prostate Cancer Early in Men with BRCA Mutations

Over the last few years, there have been a number of studies to suggest that men with BRCA mutations, particularly BRCA2, have a higher risk of developing aggressive prostate cancer. It remains uncertain whether these men might benefit from screening through the prostate-specific antigen (PSA) test. Within the last few years, PSA screening guidelines in the United States were revised, and no longer recommend screening for all men in the general population.1 However, use of the PSA test in targeted screening for high risk men remains under active study. The initial results from an international study suggested PSA screening may be useful in detecting prostate cancer early among BRCA carriers.2  Specifically, the investigators recruited almost 2500 men, of whom 59 were subsequently diagnosed with prostate cancer (including 18 BRCA1 carriers and 24 BRCA2 carriers). Based on a PSA threshold of 3.0 ng/ml, almost half of BRCA2 carriers who had a biopsy were diagnosed with prostate cancer, which is much higher than the proportions reported when screening the general population for prostate cancer. Most of the men with a BRCA2 mutation who developed prostate cancer had intermediate- or high-risk disease, which is considered to be clinically important and requires treatment. These preliminary results suggest that targeted PSA screening in BRCA carriers may be useful to detect a high proportion of those who develop aggressive prostate cancer.

1.http://www.uspreventiveservicestaskforce.org/prostatecancerscreening/prostatefinalrs.htm2. Bancroft et al.Eur Urol. 2014 Jan 15. pii: S0302-2838(14)00004-9. PMID: 24484606




ICARE Newsletter Summer 2014

Ask the Expert

The following question was addressed by Dr. Steven Narod who is a Tier I Canada Research Chair in Breast Cancer and a senior scientist at Women’s College Research Institute in Toronto, Canada.  Dr. Narod is a world-leader in the field of breast and ovarian cancer genetics. Over the course of his career, he has profoundly shaped current knowledge about cancer risks, prevention and screening amongst carriers of BRCA1 and BRCA2 mutations.

Q. As a BRCA mutation carrier, am I at an increased risk for endometrial cancer? Should I have a hysterectomy?

A. Most published studies in BRCA mutation carriers have reported that there is not a substantially higher risk of endometrial cancer. In fact, a recent report of 4456 BRCA carriers suggested that any increased incidence of uterine cancer among mutation carriers was related to the use of tamoxifen.1Results from this study indicated that even with tamoxifen use, the excess risk of endometrial cancer was small, with a 10-year cumulative risk of 2%. It has been suggested that these risks can be further reduced given the option of raloxifene (which does not raise uterine cancer risk) or aromatase inhibitors (which can be used in postmenopausal women for breast cancer prevention). As a result of our current understanding of this topic, I believe that there is no compelling reason to perform a hysterectomy to reduce the risk of uterine cancer in BRCA mutation carriers during preventive surgery to remove the ovaries and fallopian tubes. Nevertheless, it is important that the healthcare provider discuss the actual risks with the patients prior to surgery so that they can make a properly informed decision.

Segev Y, et al. Gynecol Oncol. 2013 Jul;130(1):127-31. PMID: 23562522.




ICARE Newsletter Summer 2014

New Study to Suggest Benefits of Oophorectomy in BRCA Mutation Carriers

A recent study published in the Journal of Clinical Oncology reported that prophylactic oophorectomy resulted in reducing the risk of ovarian cancer by 80%, and reduced all-cause mortality by 77%.1 The authors reported results on almost 5800 women, of whom 186 developed either ovarian, fallopian tube or peritoneal cancer. Women who had bilateral oophorectomy had a hazard ratio of 0.2 (95% CI: 0.13-0.39; p<0.001), meaning that their risk of developing ovarian cancer was reduced by 80% following the preventive removal of the ovaries. The hazard ratio for all-cause mortality to age 70 was 0.23 (95% CI: 0.13-0.39; p<0.001), which means that the risk of dying from any cause was substantially reduced by having the oophorectomy. The finding on all- cause mortality is striking and has important clinical implications. Specifically, these findings suggest the age distribution of ovarian cancers should not be the sole criterion for determining the best age at which to advise preventive surgery of the ovaries in BRCA mutation carriers. This is because removal of the ovaries may not just prevent ovarian cancer, but there may be additional benefits (particularly the reduction of breast cancer risk). However, there remain important quality of life issues to consider which need to be balanced with the probable gains in life expectancy. It is also important to note that the study did not uniformly collect information on whether the fallopian tubes were removed along with the ovaries. Nevertheless, it is now clearly evident that for the greatest reduction of ovarian cancer risk, removal of the fallopian tubes along with the ovaries is recommended. 

Furthermore, study findings imply that identifying BRCA mutations carriers in countries with limited resources to offer breast MRI screening or bilateral prophylactic mastectomy may still reduce mortality if these patients have access to salpingo-oophorectomy. Ultimately, it remains important to assess the long-term effects of removing the ovaries and fallopian tubes, and continue to work on designing effective treatments and preventive strategies.

1. Finch A et al. J Clin Oncol. 2014 May 20;32(15):1547-53. PMID: 24567435




ICARE Newsletter Winter 2014

Tamoxifen May Reduce Contralateral Breast Cancer Risk in BRCA Carriers

There have been suggestions that Tamoxifen may reduce risks for contralateral breast cancer (i.e., breast cancer in the other breast) in BRCA carriers if taken after the initial breast cancer diagnosis, based mainly on retrospective studies. Only one prospective study has looked at this question, and showed that Tamoxifen may be useful in BRCA2, but did not find an association in BRCA1 (however there were less than 20 BRCA carriers in this study, which is limiting).1 More recently, a study led by Australian researchers investigated almost 2500 women based on combined prospective and retrospective data.2 Although this was a nonrandomized design, the study was able to demonstrate that Tamoxifen use was significantly associated with a reduction in contralateral breast cancer risk in both BRCA1 and BRCA2 mutation carriers. These findings suggest that Tamoxifen may be considered for breast cancer prevention in BRCA carriers with breast tissue, particularly those who are pre-menopausal and have their ovaries. A balanced discussion of the potential benefits and harms of Tamoxifen enables these women to make an informed decision as to whether they may wish to consider this medication.

1. King MC et al. JAMA. 2001 Nov 14;286(18):2251-6. PMID: 11710890.2. Phillips KA et al.  J Clin Oncol. 2013 Sep 1;31(25):3091-9. PMID: 23918944.




ICARE Newsletter Winter 2014

Ask the Expert

The following question was addressed by Dr. Laronga who is a breast surgeon based at the Moffitt Cancer Center:

Q. What are the risks of breast cancer after ovarian cancer in BRCA carriers? What risk management options are recommended?

A. BRCA carriers remain at a higher risk of breast cancer, even after having ovarian cancer; yet there is little information as to how high this risk might be. Recently, a study of women with ovarian cancer and a BRCA mutation who were followed up for an average of almost six years showed that ~10% went on to develop breast cancer.1Thus, most women (i.e., ~90% or higher) did not develop breast cancer, even when looking at 10-year survival rates. The risk of breast cancer in women with ovarian cancer was actually lower than in BRCA carriers without ovarian cancer. Study authors suggest that non-surgical management of breast cancer risk may be appropriate for these women. At Moffitt, ovarian cancer survivors with BRCA mutations are generally offered breast cancer screening recommended by the National Comprehensive Cancer Network (NCCN).2 In addition, these women are offered consultation with a breast surgical oncologist to discuss prophylactic mastectomy after they are cancer-free five years out from their initial ovarian cancer diagnosis.

1. Domchek SM et al. Risk of metachronous breast cancer after BRCA mutation-associated ovarian cancer. Cancer. 2013 Apr 1;119(7):1344-8. PubMed PMID:23165893. 2. NCCN guidelines, 2013 Genetic/Familial High-risk Assessment: Breast and Ovarian. in NCCN Practice Guidelines V.4.2013 edn Vol. 2013 (National Comprehensive Cancer Network, Fort Washington, PA, 2013).




ICARE Newsletter Winter 2014

Contralateral Mastectomy May Improve Survival in BRCA Mutation Carriers

It has been established that women who carry a germline BRCA mutation face breast cancer risks of 60-70% in their lifetime. After an initial breast cancer diagnosis, these women face a high risk for contralateral breast cancer. Some women with BRCA mutations move forward with contralateral mastectomy when they develop their first breast cancer diagnosis (as part of their breast cancer treatment); however it remains unclear whether contralateral mastectomy reduced the breast cancer-related mortality in these women. Recently, Dr. Kelly Metcalfe published a study1 based on 390 women with stage I or II breast cancer and a BRCA mutation followed for up to 20 years from diagnosis.  Of these women, 209 were treated with unilateral mastectomy compared to 181 treated with bilateral mastectomy. Results indicated that women with BRCA-associated breast cancer treated with bilateral mastectomy were 48% less likely to die of breast cancer within 20 years of diagnosis than women treated with unilateral mastectomy (even after controlling for age).  This is among the largest and longest running studies to evaluate long-term survival of BRCA-associated breast cancers, comparing type of surgery at initial diagnosis. Study findings suggest that bilateral mastectomy should be discussed as an option for young women with a BRCA mutation and early stage breast cancer. However, despite the long follow-up and large sample size, further research is needed to confirm these findings given the small numbers of “events” (i.e., second breast cancers) in participants. Ultimately, emerging data on personalized chemotherapeutic and biologic treatments for BRCA-related breast cancers coupled with study findings suggest that women with newly-diagnosed breast cancer might benefit from the knowledge that they carry a BRCA mutation.

Metcalfe et al. 2014 BMJ. 2014 Feb 11;348:g226. PMID: 24519767




ICARE Newsletter Summer 2013

Sharing BRCA Test Results with Adolescent and Young Adult Children—What Does the Latest Research Show?

While there are specific recommendations against BRCA testing for minors,1 guidelines are less clear about whether parents should share their own test results with their children. Because there are no recommended surveillance or risk reduction options prior to age 25 for known BRCA mutation carriers, there has been debate about balancing the benefits of sharing parents’ test results with the possible negative psychosocial outcomes. The largest published study on this topic included 253 parents who had undergone BRCA testing and their reports of sharing test results with children, ranging in age from ages 10 to 25. Of the 505 children, parents shared test results with 66%. For those who shared true negative results, children often expressed relief. However, the authors encourage parents to take this opportunity to discuss the continued benefits of positive health behaviors (e.g., diet, physical activity); despite decreased cancer risk based on BRCA test results. Importantly, parents sharing BRCA positive or variant of uncertain significance results perceived distress more frequently than those sharing negative results.2 Parents considering sharing test results with children may benefit from consultation with a genetic and/or other health care professional with expertise in family communication to help ensure that information is presented in a way that is age-appropriate, helps to reduce distress, and achieves positive psychosocial and behavioral outcomes.

1. Borry P, et al. Clin Genet 70:374-81, 2006. 2. Bradbury AR, et al. Cancer, 2012.




ICARE Newsletter Summer 2013

US Preventive Services Task Force (USPSTF) Guidelines for Inherited Breast and Ovarian Cancer and Implications to the Affordable Care Act (ACA)

Recently, the USPSTF released updated draft guidelines in April 2013 (from those previously published in 2005) for inherited breast and ovarian cancer due to germline BRCA1 and BRCA2 gene mutations.1 USPSTF is comprised of primary care providers who review the available literature and issue guidelines about risk assessment, testing and management based on available evidence. Subsequently, the Department of Health and Human Services, the Department of Labor, and the Department of Treasury issued a clarification addressing coverage for BRCA testing under the Affordable Care Act (ACA). Specifically, they indicated that asymptomatic, high-risk women (as defined per the USPSTF guidelines) with a family history of breast or ovarian cancer will be able to get tested for the breast cancer risk genes BRCA1 and BRCA2 with no co-pay.2 This rule applies to non-grandfathered health insurance plans and will likely broaden access to BRCA testing, as implementation of the ACA moves forward.

1.http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrgen.html
2.http://news.yahoo.com/breast-cancer-genetic-testing-gets-covered-health-care-234648209.html




ICARE Newsletter Summer 2013

Male BRCA Carriers Have Poorer Outcomes from Prostate Cancer

Over the last few years, a number of studies have suggested that men with germline BRCA mutations (especially BRCA2) have poorer outcomes when they develop prostate cancer. In fact, a recent study of 2019 patients with prostate cancer, including 18 BRCA1 carriers, 61 BRCA2 carriers, and 1940 noncarriers indicated that germline mutations were more frequently associated with: higher Gleason score, later stage (T3/T4), nodal involvement, and metastatic disease present at diagnosis. Thus, these findings suggest that when men with BRCA mutations develop prostate cancer, it is more likely to be an aggressive subtype of the disease which may be related to the poorer outcomes observed. Consequently, study authors suggested that consideration should be given for tailoring clinical management for these patients, especially because most BRCA carriers with prostate cancer are currently treated through following the same protocols used for noncarriers (due to lack of studies focused on evaluating tailored management strategies in this group of men).

Furthermore, although clinical trials in this group are needed, authors suggested the following as a consideration: “radical treatment with either surgery or radiotherapy seems to be preferable to active surveillance for these patients, even for cases classified as low risk.”

Castro et al. J Clin Oncol. 2013 May 10;31(14):1748-57.




ICARE Newsletter Summer 2013

Oophorectomy Following Menopause

Prior studies have indicated that removal of the ovaries and fallopian tubes reduces the ovarian cancer risk by ~80% and breast cancer risk by ~50%, particularly when performed pre-menopausally. However a recent case control study of 2854 pairs of women with a BRCA1 or BRCA2 mutation with or without breast cancer showed that the risk of breast cancer was lowered more in those with surgical menopause (OR, 0.52; 95% CI, 0.40–0.66) compared to those with natural menopause (OR, 0.81; 95% CI, 0.62–1.07). Interestingly, this study also found that there was a significant reduction in breast cancer risk even in women who had their ovaries removed after they went through natural menopause (OR, 0.13; 95% CI, 0.02–0.54; P = 0.006). This is an important finding because women with BRCA mutations who remove their ovaries after menopause typically do so to lower their ovarian cancer risk – however, this study suggests that they also may be reducing their breast cancer risk at the same time. Finding from this study also highlight the importance for better understanding the protective effect of oophorectomy, as this has very important implications for chemoprevention.

Kotsopoulos J, et al. Cancer Epidemiol Biomarkers Prev. 2012 Jul; 21(7):1089-96.




ICARE Newsletter Summer 2013

BRCA Testing: Supreme Court Update

In a landmark decision regarding the patenting of human genes on Thursday June 13, 2013, the Supreme Court of the United States unanimously ruled that human genes may not be patented. The case specifically concerned the BRCA1 and BRCA2 gene patents, held by the Utah-based company, Myriad Genetics. In the ruling, Justice Clarence Thomas wrote for the court: “Myriad did not create anything. To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention.” As a result of this ruling, it is widely believed the cost of testing (currently over $4000 for full gene sequencing and large rearrangement testing when performed through Myriad) will decrease, there will be opportunities for second opinions, and innovation pertaining to BRCA testing may be enhanced. Immediately after the decision, several companies (e.g., GeneDx, Pathway Genomics, Quest Diagnostics, Ambry Genetics, DNATraits, and University of Washington) announced plans to launch tests that include the BRCA genes, at a cost as low as $995.




ICARE Newsletter Summer 2013

Ask the Expert

The following question was addressed by Dr. Pal, who is a Clinical Geneticist based at the Moffitt Cancer Center:

Q. Does exposure to radiation increase breast cancer risk in BRCA mutation carriers?

A. A number of studies have been conducted to evaluate whether BRCA mutation carriers may be more prone to radiation-induced breast cancer than women without mutations. Two studies failed to provide convincing evidence about the link between ionizing radiation exposure and breast cancer risk in BRCA mutation carriers.1,2  On the other hand, a large international study including 1601 mutation carriers reported a higher breast cancer risk among women exposed to chest X-rays (hazard ratio (HR): 1.54).  Breast cancer risk was highest among women age ≤ 40 with any x-ray exposure , and women born after 1949 with x-ray exposure before age 20.3  Some of these participants were included in a larger international study of 1993 mutation carriers where age-specific total diagnostic radiation exposure (i.e., chest x-rays, mammography, fluoroscopy, and computed tomography) was estimated from self-reported questionnaire data.4 Results indicated that those exposed before age 30 had an increased risk (HR: 1.90; 95% CI: 1.20-3.00), compared to those never exposed. However, this risk was primarily driven by non-mammographic radiation exposure in women younger than age 20 (HR: 1.62; 95% CI: 1.02-2.58).

Ultimately, it is important to weigh potential risks versus benefits regarding routine use of mammographic screening in conjunction with magnetic resonance imaging (MRI) in BRCA mutation carriers, particularly in women below age 30. As there is no clear evidence to suggest that mammograms significantly increase the breast cancer risk in BRCA mutation carriers at the current time, the main question that remains is whether mammograms are useful prior to age 30. Currently, NCCN guidelines5 recommend annual mammography and MRI screening beginning at age 25 years, although some clinics may hold off on the mammography until age 30 after a balanced discussion of risks versus benefits with patients has occurred.

1. Narod SA, et al. Lancet Oncol 7 (5): 402-6, 2006. 2. Goldfrank D, et al. Cancer Epidemiol Biomarkers Prev 15 (11): 2311-3, 2006. 3. Andrieu N, et al. J Clin Oncol 24 (21): 3361-6, 2006. 4. Pijpe A, et al. BMJ 345: e5660, 2012. 5. NCCN Practice Guidelines 2013; V.2.2013: http://www.nccn.org/professionals/physician_gls/recently_updated.asp.




ICARE Newsletter Winter 2013

Ask the Expert

The following question was addressed by Dr. Lora Thompson, a Clinical Psychologist at the Moffitt Cancer Center:                                                            

Q. How do I talk to family members about my genetic test results?

A. The ability to share risk information with family members is a common reason why many individuals undergo genetic testing. Family members may feel appreciative of the information so they can have the opportunity to learn about their personal risk of cancer and to consider cancer prevention and surveillance strategies. However, when others disagree with your decision to undergo testing, being the “gatekeeper” of genetic information can be a burden. Research on genetic test result disclosure has found that less open communication was associated with higher levels of distress in individuals undergoing genetic testing, even when their results were negative.1

 

 Below are some tips for communicating results:2,3

  • Before receiving your result, begin thinking about how, when, and with whom you will share the information.
  • Be sure that you have a good understanding of what your result means. This may be especially important if you receive a positive or uninformative result.
  • Ask your genetic counselor to help you prepare a letter or information sheet that you can provide family members.
  • Practice what you plan to say and anticipate what questions you might receive.
  • Have a trusted individual available for support.

Some families may still experience tension during the sharing process even when the tested individual practices good communication skills. In this case, consider seeking additional help from a professional with expertise in working with families, such as a psychologist, social worker, or licensed counselor. Remember that your responsibility after receiving your genetic test result is to pass on information. It is up to each family member to decide how to react emotionally and whether to pursue genetic counseling and testing.

1. van Oostrom, I, et al. Clin Genet 71, 35-42 (2007). 2. DeMarco, TA, et al. Breast Disease 27, 127-136 (2007). 3. Seymour, KC, et al. J Genet Counsel 19(4), 330-342 (2010).




ICARE Newsletter Winter 2013

Points to Consider Regarding Bilateral Salpingectomy as a Risk Reduction Procedure for Ovarian Cancer

Over the last few years, there has been evidence to suggest that a substantial proportion of ovarian cancer may start in the fallopian tubes, although some cancer clearly arises in the ovary.  As a result, removal of both fallopian tubes (called ‘bilateral salpingectomy’) has been suggested as an interim procedure to reduce risk in BRCA mutation carriers.1,2  But it is still very important to remember that there are no data available to tell us how effective this procedure is at reducing the future risk of ovarian cancer.

In essence, bilateral salpingectomy preserves ovarian function, thus it does not put premenopausal patients into premature menopause.   The procedure can be done through a minimally invasive approach, and may allow patients to defer removing their ovaries until they are closer to menopause.  In fact, a small study of 14 young BRCA mutation carriers documented the procedure as feasible.3 However, this study could not assess how effective the procedure was in reducing future ovarian cancer risk, nor was it able to assess whether the procedure had an effect on ovarian function.  Ultimately, until the usefulness of bilateral salpingectomy is more fully assessed, patients need to remember that this procedure does not eliminate their cancer risks as completely as if they had undergone a bilateral salpingo-oophorectomy (i.e. removal of both ovaries as well as the fallopian tubes).  As much as salpingectomy may become an important ovarian cancer risk reduction measure, it is exceedingly important to further study the validity of the procedure as a risk-reducing intervention in the context of research efforts.

1. Greene MH, et al. Am J Obstet Gynecol. 2011 Jan;204(1):19.e1-6. 2. Dietl J, et al. Hum Reprod. 2011 Nov;26(11):2918-24. 3. Leblanc E, et al. Gynecol Oncol. 2011 Jun 1;121(3):472-6.




ICARE Newsletter Winter 2013

The Selection of Chemotherapy in BRCA Patients with Pancreatic Cancer

Some evidence suggests that individuals with BRCA mutations who develop pancreatic cancer may benefit from specific chemotherapy regimens. In a recent review of this topic, Kim et al reported on a study of 5 patients with BRCA mutations (4 BRCA2 and 1 BRCA1) who were treated with a platinum-based chemotherapy regimen.1 Of these patients, 3 had advanced disease and all had some response to platinum; an additional 2 patients had resectable and locally advanced disease, both of whom were downstaged after receiving platinum as part of their treatment and eventually underwent resection of their tumor. Another study was conducted based on 15 BRCA carriers with pancreatic cancer.2 Of these patients, 4 received a PARP inhibitor alone or in combination with chemotherapy, of which 3 demonstrated an initial radiographic response and one patient had stable disease for 6 months. Six patients received platinum-based chemotherapy as first line treatment for metastatic disease, of whom five had a radiographic partial response.

These studies add to the limited literature to suggest that therapeutic agents that target DNA repair (e.g., PARP inhibitors, Platinum-based agents) may offer benefit when treating BRCA-associated pancreatic cancers, even in advanced stages. However, the numbers reported remain very small and it is critical to perform prospective studies in individuals with BRCA-associated pancreatic cancers to truly determine the efficacy of targeted therapies.   

1. Kim R, et al. JOP. 2012 Mar 10;13(2):180-1. 2. Lowery MA, et al. Oncologist. 2011;16(10):1397-402.




ICARE Newsletter Summer 2012

Ask the Expert: What are the risks of hormone replacement therapy (HRT) on breast cancer risk in women with BRCA mutations?

The following questions were addressed by Drs. Pal and Lancaster at the Moffitt Cancer Center:

Q. What are the risks of hormone replacement therapy (HRT) on breast cancer risk in women with BRCA mutations?

A. Concern about HRT in BRCA carriers is its potential to raise the risk of breast cancer, as seen in the general population.1-3 However, two studies in BRCA mutation carriers reported that HRT did not increase the subsequent risk of breast cancer, nor did it appear to reduce the protective effect of oophorectomy on breast cancer risk.4,5 Recent results from the Women’s Health Initiative in the general population also provide reassurance as to estrogen use for about 5 years in terms of breast cancer risk and mortality.6

1. Chen, C.L., et al. JAMA. 287, 734-41 (2002). 2. Rossouw, J.E., et al. JAMA. 288, 321-33 (2002). 3. Chlebowski, R.T., et al. JAMA 289, 3243-5 (2003). 4. Eisen, A. et al. J Natl Cancer Inst 100, 1361-7 (2008). 5. Rebbeck, T.R., et al. J Clin Oncol 23, 7804-10 (2005). 6. Anderson G.L., et al. Lancet Oncol, 13(5), 476-86 (2012).




ICARE Newsletter Summer 2012

New Study Suggests Breast Cancer Risk for Non-Carriers of Family-Specific BRCA Mutations Is Not Increased

Data from a population-based study was recently reported to estimate breast cancer risk among family members who tested negative for a known BRCA1/2 family mutation (i.e., non-carriers). The study included 3047 women diagnosed with breast cancer. Results from the study indicated there was no increased risk for breast cancer in non-carriers as compared to family members of breast cancer patients who tested negative for a BRCA gene mutation. These results support clinical practice to advise patients who test negative for family-specific BRCA mutations that their breast cancer risks are not elevated. Furthermore, in the absence of other strong risk factors, authors suggest that non-carriers should follow general population guidelines for breast cancer screening.

Kurian AW, et al. J Clin Oncol. 2011 Dec 1;29(34):4505-9.




ICARE Newsletter Summer 2012

Emerging Cancer Panels for Testing Patients for Inherited Cancer Predisposition

Genetic testing for inherited cancer predisposition is typically performed by testing for one condition at a time. However, with the tremendous advances in genetic testing technologies over the last few years, the cost of testing has plummeted. To put this into perspective, the first human genome cost 2-3 billion dollars to sequence and took over 10 years to complete. Based on newer technologies, the current cost  of sequencing a human genome is less than $10,000 and takes 4-6 weeks to complete. As such, it has become realistic to test for multiple inherited cancer conditions at the same time through “cancer panels”. These panels consist of several genes for conditions at a cost that is comparable to genetic testing for one condition. Insurance reimbursement for testing has been encouraging. An example of when to consider this test is for an individual with breast cancer in whom there is a strong family history of cancer, but the BRCA1 and BRCA2 testing (comprehensive BRACAnalysis® and comprehensive rearrangement testing (BART)) did not identify a mutation to be present. For more information about this testing, contact your local genetics professional.




ICARE Newsletter Summer 2012

Ask the Expert: What are the recommendations for screening following prophylactic surgeries?

The following questions were addressed by Drs. Pal and Lancaster at the Moffitt Cancer Center:

Q. What are the recommendations for screening following prophylactic surgeries?

A. In BRCA mutation carriers, bilateral prophylactic mastectomy reduces the risk of breast cancer by over 90%. It essentially lowers the risk of breast cancer to below that of the general population. Similarly, in those with bilateral prophylactic salpingooophorectomy (BPSO), risk of ovarian cancer is reduced by 80% or more. At the Moffitt Cancer Center, BRCA mutation carriers who have undergone a bilateral mastectomy are screened through clinical exams, and no imaging studies are routinely recommended. In those with BPSO, CA-125 levels (measured through a blood test) are ordered yearly, and no transvaginal ultrasounds are routinely recommended. These recommendations are based on clinical judgment of our team, and there is no data at this time to determine the necessity of this (or any) screening regimen in these individuals following prophylactic surgery.




ICARE Newsletter Summer 2012

Prostate Cancer Screening Recommendations for Men with BRCA Mutations

Over the last few years, there have been several studies that suggest that men with BRCA mutations are at a higher risk for developing and dying from aggressive prostate cancer. It is possible that PSA testing may be of benefit in men with BRCA mutations. However, until the utility of PSA is determined in these men, national practice guidelines continue to recommend annual prostate cancer screening (through PSA test and digital rectal exam) starting at age 40 in men with BRCA mutations. Of note, new recommendations were set forth by the U.S. Preventive Services Task Force (USPSTF) which consists of a panel of national experts. Part of their mission is to make recommendations about preventive services, such as the use of PSA screening in men. The task force revised their position on PSA screening and recently recommended against routine prostate screening for everyone. However, in May 2012, they included the following caveat: This recommendation also does not include the use of the PSA test for surveillance after diagnosis or treatment of prostate cancer and does not consider PSA-based testing in men with known BRCA gene mutations who may be at increased risk for prostate cancer.” Thus, they now indicate that those who may be at a higher risk for prostate cancer, such as BRCA mutation carriers, are not part of the recommendations and therefore it is reasonable to continue screening these individuals using the PSA test.

US Preventive Services Task Force, Moyer et al. Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2012 May. PMID: 22801674. Available at: https://www.annals.org/aim/fullarticle/doi/10.7326/0003-4819-157-2-201207170-00459