Until now our understanding of inherited breast cancer genes has been mainly limited to individuals with a personal or strong family history of the disease. Not only was a personal and family history necessary to qualify for genetic testing, but the presence of the disease was thought to be crucial evidence that the BRCA gene mutation in that family put them at a high risk for developing both breast and ovarian cancer. But, a new study published in the Proceedings of the National Academy of Sciences has turned that thinking on its head by showing that many Jewish women of Ashkenazi (Eastern European) descent carry a BRCA mutation that can cause just as high a risk of the disease even when there is no family history of breast cancer.
This study has raised a lot of serious and sensitive questions among clinicians and advocates about the complex impact of screening all Jewish women for the BRCA mutations, a move that the authors of the study have recommended.
So should all Ashkenazi Jewish women immediately be tested for the BRCA genes? No. But what they should do is to consider their unique personal circumstances and seek out the information they need to make a well-informed decision. This is also not a choice that needs to be made hastily. Women should take the time they need to make the best decision for their own situation, and if they are not ready to decide at this point in their lives, they can always reconsider testing later on.
First some facts: Ashkenazi Jewish women and men are at a much greater risk for having a BRCA gene mutation compared to the general public, but the odds are still fairly small. Among Ashkenazi Jews, 2.5 percent of females and males carry either a BRCA1 or BRCA2 gene abnormality. That means that about one in 40 Ashkenazi Jews has one of these mutations as compared to one in 400 people having a BRCA1 and one in 800 having a BRCA2 abnormality in the general population. Depending on which gene mutation (BRCA1 or BRCA2) a woman has, her chance of developing breast cancer can range between 40 percent and close to 90 percent, while her risk of getting ovarian cancer can climb to over 50 percent. (1)(2)(3)(4)
There are significant benefits to knowing if you do or do not have a BRCA mutation. If a mutation is present, you can take key prevention steps and be screened more carefully based on that knowledge. And if cancer were to occur, you could also select the most effective treatments. The information can also help your family members make more informed choices.
Prevention choices include surgeries that can substantially reduce the chance of developing these cancers. Prophylactic double mastectomies decrease the risk of breast cancer by 90 percent. (5)(6) The removal of the ovaries and fallopian tubes reduces the odds of ovarian cancer by about 80 percent and also lowers the risk of breast cancer by about 50 percent. (7)
Even for those who choose to keep their breasts or postpone their removal, knowing allows them to be closely screened every six months with alternating MRIs and digital mammography. Others may opt for medications like tamoxifen that can lower the risk of hormone receptor positive breast cancer by more than 40 percent.
However, decisions regarding genetic testing should never be made lightly. The results of these tests can require difficult and life-altering choices, for yourself and your family. Testing should only be done when you can actually use that information to take steps that will have a major positive health or life impact.
For women who are finished having children, knowing their high-risk status allows them to consider the prophylactic removal of their ovaries and fallopian tubes which, for greatest protection, is recommended be performed immediately after childbearing is completed. (8)
And for women who want to be aggressive about their care and do whatever is most effective to reduce their risk, they may opt for the removal of their breasts before cancer has a chance to occur. For them, knowing can be empowering and life-saving.
But these surgeries can also have significant physical, emotional and financial costs. And for women who are not prepared or unable to consider these tough choices, knowing can be a tremendous burden.
My advice to Ashkenazi Jewish women (of which I'm one) is to not run out and get tested, but to talk to a genetic counselor who can help you weigh your risks and your situation to determine if testing is the right and necessary thing to do.
Most women who are tested will NOT have a BRCA genetic mutation, but that does not mean that they are no longer at risk for breast cancer. It's important to know that the vast majority of breast cancers are unrelated to the BRCA genes. Whether or not you are Jewish, you can take steps to help reduce your risk of the disease by maintaining a healthy weight, exercising regularly, keeping your alcohol intake to 2-5 drinks per week (less is better) and if you're an expectant or new mom, breastfeeding your baby.
(1) Rainville, I, et al. Next-Generation Sequencing for Inherited Breast Cancer Risk: Counseling Through Complexity. Curr Oncology Rep. 16: 371. 2014.
(2) King, M. Breast and Overian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2. Science. 302, 643. 2003.
(3) Antoniou, A, et al. Average Risks of Breast and Ovarian Cancer Associated with BRCA1 or BRCA2 Mutations Detected in Case Series Unselected for Family History: A Combined Analysis of 22 Studies. Am. J. Hum. Genet. 72:1117-1130. 2003.
(4) Arindam, P, et al. The Breast Cancer Susceptibility Genes (BRCA) in Breast and Ovarian Cancers. Frontiers in Bioscience - Landmark. 19: 605-618. 2014.
(5) Heemskerk-Gerritsen, B.A.M. et al. Substantial Breast Cancer Risk Reduction and Potential Survival Benefit After Bilateral Mastectomy When Compared with Surveillance in Healthy BRCA1 and BRCA2 Mutation Carriers: A Prospective Analysis. Annals of Oncology. 24: 2029-2035, 2013.
(6) Armstrong, A. Management of Women at High Risk of Breast Cancer. BMJ. 348:g2756. 2014.
(7) Rebbeck, T, et al. Meta-analysis of Risk Reduction Estimates Associated With Risk-Reducing Salpingo-oophorectomy in BRCA1 or BRCA2 Mutation Carriers. J Natl Cancer Inst. 101:80-87. 2009.
(8) Salhab et al. BMC Women?'?s Health 2010, 10:28 http://www.biomedcentral.com/1472-6874/10/28