ICARE Social Media Post August 2020

Inherited Prostate Cancer Risk

Over 600,000 men age 40 and older who were part of a family with at least three consecutive generations affected with prostate cancer were studied from the Utah Population Database. Findings from this study showed that:

  • 36,000 had prostate cancer (5.9%)
  • 2,500 had early-onset disease (7%)
  • 4,000 had lethal disease (11.1%)
  • 15,000 had clinically significant disease (41.8%)

Investigators concluded: “In this large, population-based, family database, the risk of [prostate cancer] varied by cancer [family history] and was most strongly associated with [early-onset] disease. These results are critically valuable in understanding and targeting high-risk populations that would benefit from genetic screening and enhanced surveillance.”

Check out the original article at: https://ascopubs.org/doi/full/10.1200/JCO.19.02808

Check out the ASCO’s post about this article at: https://www.ascopost.com/news/april-2020/effect-of-familial-and-hereditary-cancer-syndromes-on-risk-of-prostate-cancer/

ICARE Newsletter Winter 2020

Community Spotlight

I was diagnosed with breast cancer in December 2018 and was found to be PALB2+. The PALB2 gene had not been tested for when my older sister was diagnosed with breast cancer and had genetic testing done four years earlier. This was new! My cancer was very similar to my sister’s, but being PALB2+ changed my treatment plan and informed me of my possible higher cancer risks for recurrence and other cancers. Like my sister, I had one small tumor in one breast. I could have just had a lumpectomy with radiation and chemo (depending on ONCA result) followed by oral medication, and then just live with a risk of recurrence. The treatment option was a skin saving, nipple sparing bilateral mastectomy with FLAP reconstruction followed by 5-10 years of oral medication. This would have reduced my risk of recurrence to below 10%.  It was a no brainer for me — I chose the latter. After my breast surgery, I was then told PALB2 was linked to ovarian cancer, so I started seeing a high-risk gynecologist. After months of discussions with my gynecologist and oncologist, I decided to have an oophorectomy. This was prompted by my PALB2 risk and my adverse reaction to Tamoxifen. The only way to get off the Tamoxifen was to put me into menopause by removing my ovaries, which at the same time, would lower my ovarian cancer risks. Again, this was a no brainer. It’s two years after my diagnosis, and I’m in a really good place. My cancer is nearly behind me, as I don’t think about it on a daily basis. I’m feeling great and look even better 😉 My energy levels are back to normal, I’m playing competitive tennis, and I’m spending time with my family traveling and enjoying life. We look to the future with positivity. We know there is a chance that I have passed the mutation onto my three kids but we feel empowered by the knowledge of knowing about it, and we will test them for it when they get older. My family is empowered too. We recently found out that my mother is PALB2+. Great news, she’s 75 years old and has never had breast cancer! So PALB2 doesn’t necessarily mean a cancer sentence! I have personally known many family and friends diagnosed with breast cancer; my best friend being one who was diagnosed 8 years ago with stage 4, triple positive, metastatic inflammatory breast cancer. She has had radiation, chemo, had her spine rebuilt, and been on numerous clinical trials. She is here today, and her tumor has shrunk by 67%. What I learned from her: “Always have a note taker with you at EVERY appointment because there is always too much info to absorb. Don’t ever give up and never let it define you. Fight your battle your way. And when you need it, ask for help.”

– ICARE Participant, Jennifer Clarke from New Orleans, LA

ICARE Social Media Post February 2020

Medication Use for Risk Reduction

Based on studies that show benefits of estrogen and androgen blockers in reducing breast cancer risk in high-risk women, the United States Preventative Service Task Force (USPSTF) recommends that clinicians offer risk-reducing medications to women at increased risk for breast cancer; however, they recommend against routine use of these medications in average-risk women.

Hormone receptor blockers (such as tamoxifen and raloxifene) and aromatase inhibitors (such as exemestane and anastrozole), reduce the risk of invasive breast cancer, but also potentially cause adverse side-effects including cataracts and bleeding disorders. Women at increased risk for breast cancer should have a conversation with their doctors to discuss the benefits and adverse effects of breast cancer risk-reducing medications.

Check out the full article at: https://tinyurl.com/ww4rf5r

and USPSTF recommendations at: https://www.ncbi.nlm.nih.gov/pubmed/31509365

ICARE Social Media Post January 2020

Ovarian Cancer Screening in BRCA1 Carriers

A new study of Polish BRCA1 carriers showed that screening through transvaginal ultrasound was not effective or  reliable in detecting ovarian cancer early. Consequently, preventive oophorectomy remains the only proven method to lower ovarian cancer risks and increase survival.

Check out the article at: https://www.ncbi.nlm.nih.gov/pubmed/31500890.

Check out the NCCN ovarian cancer screening recommendations for BRCA1 and other gene mutation carriers: https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf

ICARE Social Media Post January 2020

Polygenic Risk Scores

A Polygenic Risk Score (PRS) is calculated using genetic differences throughout someone’s DNA, in combination with clinical and family history of cancer. This unique type of score may be utilized to calculate the lifetime risk of breast cancer.

Important facts about PRS’s:

  • Different from BRCA1/2 testing, which look for changes in these specific genes
  • Should NOT be used to diagnose a hereditary cancer predisposition.
  • Should only be used in Caucasian/White women because they have not yet been studied for use in other populations.

For more information go to: https://www.ncbi.nlm.nih.gov/pubmed/30554720

ICARE Featured Video December 2019

NCCN Genetic/Familial Breast, Ovarian, and Pancreatic Guidelines

Below you may watch a featured video from the December 2019 Genetics Case Conference, which outlined updates to the National Comprehensive Cancer Network (NCCN) guidelines.


ICARE Newsletter Summer 2018

Prevention of Colorectal Cancer Among Individuals with Familial Adenomatous Polyposis (FAP)

Through a randomized trial, patients with FAP were treated with sulindac and erlotinib versus placebo for 6 months. Results of the study showed that those treated with sulindac and erlotinib had 70% fewer polyps than those in the placebo group. The lower number of polyps was seen in both those with an intact colorectum and those who had had their colon removed and only had a rectal pouch or rectum. However, there was a high rate of side effects, most commonly skin and oral mucosal findings, which may limit the use of these medications at the doses used in the current study. Additional research is needed to follow patients for a longer time period to determine the effect of these medications on patient outcomes.

Samadder NJ, et al. JAMA Oncol. 2018 May 1. PMID: 29423501.

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 Summer 2016

Cancer Chemoprevention in Individuals with Familial Adenomatous Polyposis (FAP)

Prior research has demonstrated that NSAIDs significantly reduce colonic and rectal polyp burden among individuals with FAP although their impact on outcomes remains to be determined.1,2 Recent data extended these results to the small intestine through completion of a randomized clinical trial among patients with FAP which demonstrated that use of sulindac and erlotinib compared with placebo led to lower duodenal (part of the small intestine) polyp burden at six months.3 However, grade 1 or 2 adverse events (i.e., side effects) were more common in the group that received the drug (the majority of which included an acne-like rash) which may limit use of these medications at the doses given in this study. Given results of this preliminary study, it is important to evaluate these drugs in a larger population of patients with FAP with a longer follow-up period to determine if these observations lead to improved clinical outcomes among these individuals.

1Giardiello FM, et al. N Engl J Med. 1993;328(18):1313-1316.PMID: 8385741.
2Giardiello FM, et al. N Engl J Med. 2002;346 (14):1054-1059.PMID:11932472.
3Samadder NJ, et al. JAMA. 2016 Mar 22-29;315(12):1266-75.PMID: 27002448.

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 Summer 2015

Advances in Preventive and Treatment Approaches for Individuals with Lynch Syndrome

A study of over 1800 individuals with a mutation in one of the Lynch Syndrome genes was recently completed to assess whether aspirin and ibuprofen use may reduce colon cancer risk. Results showed that in those who took aspirin or ibuprofen for between 1 month and 4.9 years, the colon cancer risks were lower than those with less than one month of use.  This study provides additional evidence that both aspirin and ibuprofen may be an effective strategy to help reduce colorectal cancer risk among those with Lynch syndrome, where individuals currently rely solely on frequent colonoscopies for risk reduction. We encourage patients to speak with their healthcare provider about this study to determine if the addition of these medications would be right for them.

Pertaining to treatment of colorectal cancers, a new class of drugs that target the immune system (called PD-1 Inhibitors) has been shown to have potential efficacy in colorectal cancers with the MSI-H phenotype.  Given that most colorectal cancers in individuals with Lynch syndrome are MSI-H, this drug could potentially represent a targeted treatment for these individuals.  However, prior to becoming standard treatment in the clinical setting, clinical trials are needed.  These are currently being conducted to evaluate PD-1 inhibitors in individuals with MSI-H colorectal cancers. As clinical trials continue, we will monitor this exciting advancement for individuals with Lynch Syndrome.

 Ait Ouakrim D et al. Aspirin, Ibuprofen, and the Risk of Colorectal Cancer in Lynch Syndrome. J Natl Cancer Inst. 2015 Jun 24;107(9). PMID: 26109217

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

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 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 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 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.