Preventing cancer among BRCA mutation carriers by surgery

20 September 2010

People with mutations in the BRCA1 or BRCA2 genes are at greatly increased risk of developing breast and ovarian cancers compared with the general population. Mutation carriers may receive increased levels of screening to detect tumours (more effective for breast than ovarian cancers), or they may opt for preventative surgery to remove the breasts (mastectomy) or ovaries (oophorectomy). Major surgery of this kind is not undertaken lightly, but a significant number of women make this choice.
A new prospective study reports on the effect of preventativemastectomy and oophorectomy procedures in women with BRCA mutations [Domchek SM et al. (2010) JAMA 304(9):967-75]. The research involved a total of nearly 2500 women from centres in Europe and the US, looking at cases of breast and ovarian cancer, rates of cancer-related deaths, and overall mortality rates. Women who had preventative surgery of any kind, or ovarian cancer prior to enrolment in the study were excluded.
There were no breast cancers diagnosed in the 247 women who had had mastectomies over a three-year period, compared with 98 cases among the 1372 women who did not (around 7%), suggesting a significant risk reduction for breast cancer from the surgery.
A more complex picture was examined for oophorectomies. Of women who had this procedure, 1.1% developed ovarian cancer and 11.4% developed breast cancer, compared with 5.8% and 19.2% of those who did not have the surgery, respectively. The risk of death from both ovarian and breast cancers was reduced following oophorectomy, as was the overall mortality rate at 3.1% (compared with 9.8% among women who did not have surgery).
A significant decrease in the risk of ovarian cancer was observed for mutation carriers with and without previous breast cancers, and in the risk of breast cancer for carriers who had not previously had breast cancer, but the risk of subsequent breast cancers in those who had already had a primary breast cancer was not apparently reduced by oophorectomy.

Comment: Although this study has many limitations and leaves various questions unanswered, it does show that there is a genuine protective benefit from mastectomy and oophorectomy surgery for high-risk BRCA mutation carriers. This useful information should be weighed against alternative options – increased screening and chemoprevention – including the health risks of surgery, and premature menopause associated with the loss or suppression of ovarian function. 

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