GYNECOLOGIC ONCOLOGY

In the analysis of the matched BRCA mutation carriers, women who chose to undergo the procedure had a decreased risk of overall mortality (hazard ratio [HR]=0.24; 95% confidence interval [CI], 0.08–0.71); they also had a decreased risk of mortality due to both breast cancer (HR=0.1; 95% CI, 0.02–0.71) and ovarian cancer (HR=0.05; 95% CI, 0.01–0.46).

Practice recommendations

Apparently, unlike women at average risk of ovarian cancer (for whom prophylactic oophorectomy in conjunction with hysterectomy for benign disease may be associated with decreased overall survival; see the review of the study by Parker and colleagues), women with BRCA mutations may benefit from oophorectomy.

Advantages of prophylactic bilateral salpingo-oophorectomy in this patient population should be discussed with potential surgical candidates, because:

• Women who have a BRCA mutation and who have had bilateral salpingo-oophorectomy were shown to have improved overall and cancer-specific survival.
• In this specific group of BRCA mutation carriers, this study did not demonstrate an increased risk of mortality from cardiovascular disease, osteoporosis, or other causes associated with premature menopause from bilateral salpingo-oophorectomy.

In BRCA carriers, HRT after oophorectomy does not raise breast cancer risk

Rebbeck TR, Friebel T, Wagner T, et al; for the PROSE Study Group. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2005;23:7804–7810.

In women with BRCA1 or BRCA2 mutations, the risk of ovarian cancer is staggering (20% to 40% for BRCA1 mutations, 15% to 25% for BRCA2 mutations), and prophylactic bilateral salpingo-oophorectomy is the only strategy proven to significantly reduce risk. A second important benefit for bilateral salpingo-oophorectomy among premenopausal mutation carriers is that the procedure decreases the risk of breast cancer by 50%. In women who have a lifetime risk of breast cancer that is as high as 80%, this benefit is extremely welcome. Current recommendations are for women with BRCA1 or BRCA2 mutations to undergo bilateral salpingo-oophorectomy at age 35 to 40, or when child-bearing is complete.

Yet, for many women in this age group, quality of life is substantially altered when premature menopause kicks in after the surgery. Most ObGyns feel comfortable giving short-term hormone replacement therapy (HRT) after prophylactic bilateral salpingo-oophorectomy to premenopausal women who do not have a history of breast cancer. However, until this study, no data were available that addressed the question of whether short-term HRT affects breast cancer risk.

In a prospective cohort of 462 women, of whom 155 underwent bilateral salpingo-oophorectomy, Rebbeck and colleagues evaluated the risk of developing breast cancer over an average of 3.6 years based on exposure to any type of HRT. In this multicenter study conducted at 13 different institutions in the United States and Europe, they found that women who underwent bilateral salpingo-oophorectomy for a BRCA1 or BRCA2 mutation were more likely to be older, have had children, and were more likely to use HRT. Compared with women who did not have bilateral salpingo-oophorectomy, women who had undergone the procedure and used any short-term HRT (including estrogen, progesterone, or a combination) still had a substantial decrease in breast cancer risk (HR=0.37; 95% CI, 0.14–0.96).

Practice recommendations

We can now reassure young women who must decide whether to undergo prophylactic bilateral salpingo-oophorectomy to reduce their staggering risks of breast and ovarian cancer: Short-term HRT to address the hot flashes, night sweats, and vaginal dryness associated with premature surgical menopause, first, is clinically reasonable and, second, will not substantially reduce the benefits of bilateral salpingo-oophorectomy for breast cancer risk.