ICARE Social Media Post July 2020

Updates to 2020 NCCN Genetic/Familial Colorectal Guidelines

The National Comprehensive Cancer Network (NCCN) released new guidelines for 2020 on July 21, 2020. The big changes included refining some of the risks for genes involved in Lynch Syndrome, and providing specific guidance about cancer screening that may slightly differ by gene.

You can check out the full guidelines by creating a FREE account at: https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.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 Social Media Post February 2020

Advances in Treatment: Plexiform Neurofibromas in NF1

The FDA has granted a breakthrough therapy designation to selumetinib, a MEK inhibitor, for treatment of inoperable plexiform neurofibromas.

These types of neurofibromas are almost exclusively seen in individuals with neurofibromatosis type 1 (NF1). These plexiform neurofibromas are benign tumors on the nerve sheaths and can develop anywhere in the body. These tumors typically cause morbidities such as pain, motor dysfunction, disfigurement, and more, and can surround internal organs. Approximately 5-10% can transform to malignant peripheral nerve sheath tumors. Although many of them can be removed through surgery, there are some that are inoperable.

A recent study showed that most patients with inoperable plexiform neurofibromas had some benefit with treatment with selumetinib which may represent a tremendous treatment advance for these individuals.

Check out more information about this study at https://ccr.cancer.gov/news/article/mek-inhibitor-selumetinib-granted-breakthrough-designation-by-fda-to-treat-neurofibromatosis-type-one-in-pediatric-patients




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

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 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 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 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 Newsletter Summer 2019

Updates to National Comprehensive Cancer Network (NCCN) Genetic/Familial High-Risk Assessment: Colorectal Guidelines

(Version 1.2019, posted July 3, 2019)

For Individuals with Lynch Syndrome:

  • The cancer risk table was updated:
    • Addition of new cancer risks by specific genes: breast and bladder cancers
    • Updates of cancer risks by specific genes: ovarian, prostate, gastric, pancreatic, urothelial, small bowel, and brain/CNS cancers
    • Removal of reference to sebaceous neoplasms
  • Recommendations for cancer risk management were updated for colon, gastric, small bowel, urothelial, and prostate cancers:
    • For MSH6 carriers: consideration of colonoscopy at age 30 y or 10 y younger than age of any relative with colorectal cancer
    • Initiation of gastric and small bowel cancer surveillance was updated to 40 y
    • Surveillance for urothelial cancer may be considered in individuals with a family history of urothelial cancer or MSH2 mutations (especially males)

For Individuals with Attenuated Familial Adenomatous Polyposis (AFAP) and MUTYH-Associated Polyposis:

  • Colonoscopy frequency was increased to every 1-2 y

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




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 2018

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

(Version 1.2019, posted July 11, 2018)

  • Regardless of family history, some individuals with a hereditary breast- and ovarian-related cancer may benefit from genetic testing to determine eligibility for targeted treatment
  • The multi-gene testing section table was updated with:
    • A potential association of ATM with ovarian cancer risk
    • Potential increased risk of BARD1 with breast cancer
    • Risk of breast cancer in BRIP1 was changed from no increased risk to unknown/insufficient evidence

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




ICARE Newsletter Summer 2018

Updates to NCCN Genetic/Familial High-Risk Assessment: Colorectal Guidelines

For Individuals with Lynch Syndrome:

  • Surveillance for gastric and small bowel cancer now indicates there is no clear data to support this, but surveillance can be performed every 3-5 years starting at age 40
  • Lack of evidence to make a recommendation for pancreatic or prostate cancer screening, beyond those already recommended through other NCCN Guideline panels
  • Increased breast cancer risk was acknowledged, however there is not enough evidence to support increased screening above what is recommended for the general population

In the multi-gene testing section:

  • New genes added for colorectal cancer risk included NTHL1 and MSH3 (‘biallelic’ mutations)
  • Indicated lack of data to determine screening recommendations among those with single (heterozygous) mutation in MUTYH and a second degree relative with colorectal cancer

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




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

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 Summer 2017

Emerging FDA Approvals of Immunotherapy Among Patients With Metastatic MSI-H Cancers

Over the last few years, immunotherapy has emerged as an exciting new class of drugs. As early as 2015, immunotherapy through PD-1 Inhibitors among patients with MSI-H colorectal cancers was shown to be of potential benefit.1 As many individuals with Lynch Syndrome have cancers that are MSI-H and mismatch repair deficient, this class of drugs was thought to represent a class of ‘targeted treatments’ for individuals with this syndrome.

More recently, the FDA granted accelerated approval for the use of a PD-1 Inhibitor (nivolumab) for the treatment of patients with MSI-H or mismatch repair deficient metastatic colorectal cancer that has progressed after standard treatment through fluoropyrimidine, oxaliplatin, and irinotecan.2 The approval was based on results of the Phase II CheckMate-142 trial, where almost a third of patients who received nivolumab experienced some benefit from it.3 These exciting advances illustrate the expanded treatment options that are being evaluated and approved for those with inherited forms of cancer.

1Le et al. N Engl J Med. 2015 Jun 25;372(26): 2509-20. PMID:26028255.
2https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-receives-fda-approval-opdivo-nivolumab-ms.
3Overman et al. Lancet Oncol. 2017 Jun 19. [Epub ahead of print] PMID: 28734759.




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

NCCN Guidelines Version 1.2017: Genetic/Familial High-Risk Assessment: Breast and Ovarian

Additional guidance pertaining to cancer risk management was provided in the most recent version of the NCCN Guidelines for inherited breast and ovarian cancer. These guidelines now include an expanded table outlining cancer risks and management for each gene, taking into account the age at initiation of each risk management modality as well as footnotes to highlight some of the nuances concerning particular mutations in specific genes. For example, among ATM and CHEK2 carriers, recommended age at initiation of high-risk breast screening with breast MRI is 40 years. Furthermore, the higher breast cancer risks associated with the ATM 7271T>G missense mutation is included as a footnote, as is the fact that the data on increased breast cancer risks associated with NBN is almost solely derived from the 657del5 truncating mutation. The full guidelines may be accessed through the NCCN website (www.nccn.org).




ICARE Newsletter Summer 2016

Practice Guideline Updates for NCCN Genetic/Familial High-Risk Assessment

The National Comprehensive Cancer Network (NCCN) is a network of oncology healthcare providers who work together to develop best practice guidelines for the delivery of cancer care. Given the increasing use of testing for mutations in several inherited cancer genes at one time (called “multi-gene panel testing”), the Breast/Ovarian and Colorectal Panels sought to provide medical management guidance when using this testing approach. To access current NCCN guidelines, visit: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp.

Breast and Ovarian (v2.2016)

Cancer risk management recommendations for some of the newer inherited breast and ovarian cancer genes were recently added. Based on emerging data, risk-reducing salpingo-oophorectomy became a consideration for women with mutations in BRIP1, RAD51C and RAD51D. Also, risk-reducing mastectomy became a consideration for women with a PALB2 mutation.




ICARE Newsletter Summer 2016

Practice Guideline Updates for NCCN Genetic/Familial High-Risk Assessment

The National Comprehensive Cancer Network (NCCN) is a network of oncology healthcare providers who work together to develop best practice guidelines for the delivery of cancer care. Given the increasing use of testing for mutations in several inherited cancer genes at one time (called “multi-gene panel testing”), the Breast/Ovarian and Colorectal Panels sought to provide medical management guidance when using this testing approach. To access current NCCN guidelines, visit: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp.

Colorectal (v1.2016)

The current version was significantly changed to include risk level and recommended management for several newer genes associated with colorectal cancer risk as outlined below:

  • High-Risk Colorectal Cancer Genes (GREM1, POLD1, POLE): Begin colonoscopy between age 25-30 and repeat every 2-3 years if normal. If polyps are found, repeat colonoscopy every 1-2 years. Surgical consideration if polyp number becomes unmanageable.
  • Low/Moderate-Risk Colorectal Cancer Genes (APC (I1307K variant), BLM (single carrier), CHEK2, GALNT12, MUTYH (single carrier)): For carriers without a personal history of colon cancer who have a first-degree relative (parent, sibling, child) with colorectal cancer: colonoscopy every 5 years beginning at age 40 or 10 years prior to the earliest diagnosis of colon cancer in the first-degree relative. For patients without a personal history of colon cancer who do not have a first-degree relative with colorectal cancer: colonoscopy every 5 years beginning at age 40.
  • Lynch Syndrome (LS) (MLH1, MSH2, MSH6, PMS2, EPCAM): Begin colorectal screening at the same age and interval regardless of which of the five LS genes has a mutation. This is an important update for individuals with LS to share with at-risk family members as this may help to inform the age at which relatives may consider predictive testing for a known familial mutation. The updated NCCN colorectal cancer screening guidelines for LS are as follows:

LS Genes

Colorectal Cancer Risk
by Age 70

Updated Colorectal Cancer Screening

MLH1, MSH2, MSH6, PMS2, EPCAM
  • MLH1/MSH2: 52-82% 
  • MSH6: 10-22%
  • PMS2: 15-20%
  • Begin colonoscopy at 20-25 years old or 2-5 years prior to the earliest colon cancer in the family if diagnosed < age 25
  • Repeat every 1-2 years



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 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

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

Genetic/Familial High-Risk Assessment: Colorectal Guidelines

  • Recommendation that tumors from newly diagnosed colorectal cancer patients be screened for Lynch syndrome (called “Universal Tumor Screening”).
  • A new algorithm was created for Routine Tumor Testing Criteria for Lynch Syndrome
  • Surveillance/Management recommendations were refined by gene for the various Lynch Syndrome genes.
  • Management recommendations were refined for other inherited colorectal cancers, including Familial Adenomatous Polyposis, Peutz-Jeghers Syndrome, Juvenile Polyposis Syndromes, and Colonic Adenomatous Polyposis of Unknown Etiology.

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




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 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

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 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