BRCA Mutation Carriers

Association of Risk-Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers With Cancer Risk and Mortality

Domchek SM, Friebel TM, Singer CF, et al.

JAMA. 2010;304:967–975

In some ways, the discovery that a woman carries the BRCA gene mutation is the ultimate triumph of screening. By identifying women who are much more susceptible to breast and ovarian cancer than those without the mutation, geneticists have achieved the holy grail of risk identification.

Women inheriting the BRCA1 or BRCA2 mutation have a greater than 50% chance of developing breast cancer in their lifetime as well as a 33% to 66% chance of developing ovarian cancer with the BRCA1 mutation and a 10% to 25% chance with BRCA2 mutation.

These are major risks capable of provoking personal, familial, and financial fears that need to be dealt with in a highly professional manner. Family or personal history can trigger BRCA testing and, because of the cross-correlation of risk, any woman diagnosed with one cancer should be BRCA tested to estimate her risk of the “alternate” malignancy.

Having been diagnosed as a BRCA carrier, the woman has to decide between increased surveillance, medical therapy, chemotherapy, or risk-reducing prophylactic surgery. In the case of breast cancer, raised surveillance levels mean more frequent imaging than usual, possibly mammography plus breast magnetic resonance imaging alternating every 6 months, but screening for ovarian cancer with cancer antigen 125 and ultrasound scanning is of limited value, no matter what the frequency.

At the other end of the spectrum, risk-reducing mastectomy and risk-reducing salpingo-oophorectomy carry considerable promise. Skillful mastectomies have cosmetically pleasing outcomes and minimally invasive laparoscopic salpingo-oophorectomy is not as formidable as it was a decade ago. The results of preventive surgery are encouraging and lower the risks substantially. But the decision is not trivial nor is the timing easy in relation to child-bearing, menopause, other cancers, age, and facilities available. The authors’ results were excellent, but only 10% of BRCA-positive women chose risk-reducing mastectomy and 40% chose risk-reducing salpingo-oophorectomy. Perhaps their positive data will move more candidates toward radical treatments.