Use of hormone replacement therapy following bilateral risk-reducing oophorectomy in women with BRCA1/2 mutations

Bilateral risk-reducing oophorectomy (BRRO) is widely used for cancer risk reduction in women with BRCA1/2 mutations.  BRRO reduces breast cancer risk by approximately 50% and ovarian cancer risk by 85-95% (1,2).  However, this surgery induces premature loss of ovarian function which may be accompanied by menopausal symptoms, impaired quality of life, and accelerated bone loss. Therefore, decisions regarding the timing of BRRO, the risks and benefits of a simultaneous hysterectomy, and the use of hormone replacement therapy must be made in concert with the patient and individualized to their circumstances. 

Recent data demonstrate that hormone replacement therapy following BRRO in unaffected premenopausal women does not negate the breast cancer risk reduction that BRRO provides (3). 

Based upon the literature available to date, women with BRCA1/2 mutations should be discouraged from deferring BRRO because of fear of symptoms related to surgical menopause and should be reassured that use of short term hormone replacement, if needed to manage menopausal symptoms, does not negate the breast cancer risk reduction from BRRO.  BRRO, even with short-term HRT, results in dramatic reductions in both breast and ovarian cancer risk.

References

1. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van't Veer L, Garber JE, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002;346(21):1616-22.

2. Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2002;346(21):1609-15.

3. Rebbeck TR, Friebel T, Wagner TM, Lynch H, Garber J, Daly M, et al. Effect of short term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 2005; 23(31):7804-10.

Timothy R. Rebbeck

University of Pennsylvania School of Medicine, Philadelphia, PA