Breast and Ovarian Cancer Risk Reduction Overview for Women with BRCA1 or BRCA2 Mutations

Two main approaches to reduce cancer risk in women with a documented BRCA1 or BRCA2 mutation are generally considered.  The strategies both involve “prophylactic” or “risk-reducing surgery”.  Although neither of the main strategies has been tested in gold-standard randomized clinical research trials, there is substantial evidence now supporting the prevention efficacy of these approaches.

Prophylactic Mastectomy (aka Risk-Reducing Mastectomy) Decreases Breast Cancer Risk in Women with BRCA1/2 Mutations*

One of the major prevention tools that women with BRCA1/2 mutations have available to them is prophylactic (also known as risk reducing) mastectomy.  A number of studies have provided evidence demonstrating that Risk-Reducing Mastectomy (RRM) is highly effective in reducing the risk of breast cancer in women with HBOC.  Although it is quite effective in this context, it is not completely effective, ultimately preventing perhaps 90 percent of breast cancers in women with BRCA1 and BRCA2 mutations.

RRM rates vary significantly from country to country and geography to geography.  For a woman with a BRCA1 or BRCA2 mutation, the decision about whether or not to undergo RRM is highly personal and one that should be discussed extensively with your physician, considering both your own personal thoughts about approaches to cancer prevention and your physician’s recommendations.  It is also important to consider reconstruction options during the decision-making process.  We’ll be adding more informational and educational resources here related to RRM in the future.

Risk-Reducing (aka Prophylactic) Salpingo-Oophorectomy*

Risk-reducing salpingo-oophorectomy (RRSO), which is surgical removal of the ovaries and fallopian tubes, is increasingly recommended to and pursued by women with HBOC after they have completed childbearing.  The reasons are two-fold.

First, RRSO – not surprisingly – substantially decreases the risk of diagnosis of ovarian cancer for women with HBOC.  Although randomized controlled trials of RRSO have not been performed (and won’t ever be performed because they would be unethical now), the available evidence suggests that this procedure can decrease ovarian cancer-specific death by about 95 percent.  Additionally, because of hormonal effects, it can cut the high risk of breast cancer in HBOC roughly in half.

For these reasons, RRSO has increasingly been very strongly recommended to women with BRCA1 and BRCA2 mutations, with a goal of performing it in the 35-40 year old age range for optimal preventative effect (and after having kids if the woman desires).

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* We will be expanding the information about risk reduction available at BRCAscoop significantly over the coming month with more information both here and in a Q&A section.  Additionally, stay tuned to our blog for information about new studies relevant to risk reduction as they get published.

Some Key References

Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality.  JAMA 2010; 304:967-75.

Eisen A, Lubinski J, Klijn J, et al. Breast cancer risk following bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers.  Journal of Clinical Oncology 2005; 23:7491-6.

Finch A, Beiner M, Lubinski J, et al. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation.  JAMA 2010; 296:185-92.

Hartmann LC, Schaid DJ, Woods JE, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer.  New England Journal of Medicine 1999; 340:77-84.

Hartmann LC, Sellers TA, Schaid DJ, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers.  Journal of the National Cancer Institute 2001; 93:1633-7.

Kauff ND, Domchek SM, Friebel TM, et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study.  Journal of Clinical Oncology 2008; 26:1331-7.

Kramer JL, Velazquez IA, Chen BE, et al. Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers.  Journal of Clinical Oncology 2005; 23:8629-35.

Kurian AW, Sigal BM, Plevritis SK.  Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers.  Journal of Clinical Oncology 2010; 28:222-231.

Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation.  New England Journal of Medicine 2001; 345:159-64.

National Comprehensive Cancer Network.  Clinical practice guidelines in oncology genetic/familial high-risk assessment: breast and ovarian.  Version 1. 2010.  http://www.nccn.org/professionals/physician_gls/PDF/genetics_screening.pdf.

Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group.  Journal of Clinical Oncology 2004; 22:1055-62.

Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers.  Journal of the National Cancer Institute 2009; 101:80-7.

Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations.  New England Journal of Medicine 2002; 346:1616-22.