Salpingo oophorectomy — the removal of ovaries and fallopian tubes — has long been considered to be a means of preventing ovarian cancer in woman with genetic susceptibility to this disease. But until now, little clinical data has supported the efficacy of this approach. Two recent studies published in the New England Journal of Medicine report that this procedure can decrease the incidence of breast cancer and gynaecological cancers in women carrying BRCA mutations.

The BRCA1 and BRCA2 genes encode proteins that participate in the DNA-damage response, and mutations in these genes have been associated with increased susceptibility to breast and ovarian cancers. These mutations contribute to a small fraction of breast cancer cases, but make up 10% of cases diagnosed in women under 40 and almost 75% of all familial cases. Furthermore, about 10% of all ovarian cancer cases are associated with BRCA mutations. As BRCA genetic tests are available, preventative measures are needed for patients that test positive for cancer-associated mutations. Carriers of BRCA1 mutations have a 50–85% lifetime risk of developing breast cancer and a 20–40% lifetime risk of ovarian cancer, whereas women with BRCA2 mutations have a 10–20% risk of developing ovarian cancer.

Bilateral prophylactic mastectomy has been shown to prevent cancer in these women, but concern about the fact that breast cancer does not develop in all carriers, and the knowledge that early cancers can be treated effectively, have made this a controversial preventative approach. Although risk of ovarian cancer in carriers of BRCA mutations is lower than the risk of breast cancer, the absence of reliable methods for early detection and the high mortality rates for advanced ovarian cancer indicate that prophylactic oophorectomy might be a good option. Fortunately, because oophorectomy is not usually diagnosed until women are in their 50s, prophylactic oophorectomy can be delayed until after a woman's child-bearing years are completed.

Data from two large clinical studies now support this theory. Noah Kauff et al. reported the results of a prospective study of 170 BRCA-mutation carriers. Of 72 women who elected intensive surveillance, 6.9% developed ovarian cancer or papillary serous carcinoma of the peritoneum. Of the 98 women who underwent prophylactic salpingo oophorectomy, however, three had early-stage tumours that were diagnosed at the time of surgery, and primary peritoneal cancer developed in one patient during follow-up (1%). Breast cancer developed in 12.9% of women in the surveillance group, but only in 4.3% of women in the oophorectomy group.

In an accompanying article, Tim Rebbeck et al. reported the results of a multicenter retrospective analysis of 551 BRCA-mutation carriers. Ovarian cancer developed in 20% of women who chose to undergo surveillance. In women that chose the surgery, stage I ovarian tumours were identified at the time of surgery in six women (2.3%), and primary peritoneal cancer only developed in two others (0.8%). During 11 years of follow-up, breast cancer developed in 42.3% of women who underwent surveillance, but only 21.2% of women who had undergone prophylactic oophorectomy.

Why does oophorectomy prevent breast cancer? The ovaries produce oestrogen, and oestrogen-receptor signalling promotes proliferation of breast tumour cells. Not all BRCA-associated tumours express high levels of the oestrogen receptor, however, so the protective effects of oestrogen antagonists in BRCA-mutation carriers have been debated.

The findings of Kauff and Rebbeck indicate that hormonal manipulation does indeed have a preventative effect on BRCA-associated cancer. The preventative effect did not, however, require a complete oestrogen blockade, as many of the women in the study received hormone-replacement therapy. But the ability to prevent breast and ovarian cancer in BRCA-mutation carriers will encourage genetic testing of women with a family history of breast cancer.