Risk-Reducing Salpingo-Oophorectomy and BRCA: Retain the Uterus?

July 21, 2016

Risk-Reducing Salpingo-Oophorectomy and BRCA: Retain the Uterus?

  1. Andrew M. Kaunitz, MD

Multicenter study suggests that hysterectomy should be encouraged in BRCA mutation carriers.

  1. Andrew M. Kaunitz, MD

In women who harbor BRCA mutations, risk-reducing salpingo-oophorectomy (RRSO) is routinely recommended to lower risk for ovarian and breast cancer — but whether this surgery should include hysterectomy remains unclear. Investigators prospectively evaluated risk for uterine cancer in BRCA1 and BRCA2 mutation carriers who underwent RRSO without hysterectomy at one of nine centers in the U.S. or U.K. and compared this risk with expected rates from national surveillance data. Observed-to-expected (O:E) ratios (similar to relative risk) were calculated.

Among 1083 women (median age at RRSO, 46; median follow-up, 5 years), 8 incident uterine cancers occurred (expected incidence, 4.3; O:E ratio, 1.9; P=0.09). In analysis stratified by tumor subtype, no excess risk for endometrioid endometrial cancer or sarcoma was observed. Five serous and/or serous-like endometrial cancers occurred after RRSO (4 in BRCA1 carriers, 1 in BRCA2 carriers), yielding O:E ratios of 22.2 for BRCA1 carriers (P<0.001) and 6.4 for BRCA2 carriers (P=0.15).

Comment

Although adding hysterectomy to RRSO increases risk for perioperative complications, use of minimally invasive approaches should attenuate this risk. Women with serous endometrial cancer have worse outcomes than those with endometrioid endometrial tumors, even when diagnosed at an early stage. Future risk for uterine malignancy is essentially eliminated by hysterectomy. Risk-reducing gynecologic surgery in BRCA mutation carriers is optimally performed before age 40; and unless hormone therapy is used, severe menopausal symptoms likely occur and women are at excess risk for osteoporosis as well as cardiovascular and neurodegenerative disease. Given that hysterectomy allows estrogen (little or no effect on breast cancer risk) to be prescribed without progestin (small elevation in breast cancer risk), hysterectomy has particular advantages for younger mutation carriers undergoing risk-reducing gynecologic surgery. I agree with the editorialists: Provided a minimally invasive approach is used, we should encourage hysterectomy as part of risk-reducing surgery for BRCA mutation carriers.

Editor Disclosures at Time of Publication

  • Disclosures for Andrew M. Kaunitz, MD at time of publication Consultant / Advisory board Allergan; Bayer AG; Merck; Pfizer Royalties UpToDate Grant / Research support Therapeutics MD; Bayer; Agile; Merck Editorial boards Contraception; Menopause; Contraceptive Technology Update; OBG Management; Medscape OB/GYN & Women’s Health Leadership positions in professional societies North American Menopause Society (Board of Trustees)

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