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Risk-reducing Surgery

Risk Reducing Surgery Lowers Likelihood of Breast and Ovarian Cancer; Decreases Mortality of BRCA and BRCA Mutation Carriers.

by Lisa Rezende, PhD

The question haunts all women who learn they carry a BRCA mutation: what do I do now? One choice many women make is to remove their ovaries and/or breasts to reduce their risk of ovarian and breast cancers. While this choice seems like a "no-brainer" to some high-risk women, it is not without controversy, as these surgeries carry risks and consequences. A new study reported in the Journal of the American Medical Association shows that risk-reducing surgeries not only decrease cancer risk but also increase the life span of BRCA1/2 mutation carriers.

Gathering a large cohort of women is critical to address common questions such as 'Is a given strategy more effective for BRCA1 mutation carriers than BRCA2 mutation carriers?' or 'Is one strategy more effective than another in preventing cancer or prolonging survival in mutation carriers?' This published study is particularly meaningful because enough patients participated to allow researchers to analyze the effects of risk-reducing surgeries by mutation status and look at the effect on previvors (unaffected carriers) as well as survivors.

Over 2,000 women participated; about half chose to undergo one or more risk-reducing surgery. The compelling results showed that risk-reducing surgeries significantly reduced cancer diagnoses, and that risk-reducing removal of ovaries lowered cancer-related deaths:

  • Risk-reducing mastectomy was associated with a decreased chance of breast cancer in women with BRCA1/2 mutations. None of the study participants were diagnosed with breast cancer in the three years after their mastectomy. In contrast, about 7% of women who did not undergo risk-reducing mastectomy were diagnosed with breast cancer during the same period.
  • Risk-reducing removal of ovaries and fallopian tubes lowered the risk of ovarian cancer and primary peritoneal cancer (a cancer closely related to ovarian cancer) in both BRCA1 and BRCA2 mutation carriers. While none of the BRCA2 mutation carriers developed primary peritoneal cancer after surgery, 1.8% of BRCA1 mutation carriers did. This is still a significant reduction in risk from the 7.4% of women who did not undergo prophylactic oophorectomy and were diagnosed with ovarian cancer during the course of the study.
  • Removal of ovaries was also associated with a decreased risk of breast cancer in both BRCA1 and BRCA2 mutation carriers who were not previously diagnosed. However, removal of ovaries did not reduce the risk of recurrence in BRCA1 and BRCA2 mutation carriers who were previously diagnosed with breast cancer.

We know that these surgeries reduce risk, but do they extend lives? This study showed that risk-reducing surgeries reduced mortality due to cancer for both BRCA1 and BRCA2 mutation carriers. Prophylactically removing the ovaries was associated with a statistically significant reduction of mortality from all causes in BRCA1 mutation carriers. Unfortunately, researchers were unable to make the same conclusion about BRCA2 mutation carriers because too few participated in the study. An editorial in the same issue of the Journal of the American Medical Association explains that the compelling results of this study reinforce the need for early identification of women at risk for carrying BRCA1 or BRCA2 mutations whether or not they have been diagnosed with cancer, and calls for primary care physicians to be educated on identifying at-risk patients and providing referrals to certified genetic counselors.

References

Domchek, SM et al., "Association of Risk- Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers with Cancer Risk and Mortality." Journal of the American Medical Association (2010); 304:967-975.

Esserman, Laura and Kaklamani, V. "Lessons Learned from Genetic Testing." Journal of the American Medical Association (2010); 304:1011 - 1012.

Lisa Rezende, Ph.D., is a lecturer in the Department of Chemistry and Biochemistry at the University of Arizona.

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