Expert Commentary

Should risk-reducing gynecologic surgery for BRCA mutation carriers include hysterectomy?

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Q: Should risk-reducing gynecologic surgery for BRCA mutation carriers include hysterectomy?

A: Yes, hysterectomy should be encouraged for women with BRCA mutations planning to undergo risk-reducing salpingo-oophorectomy (RRSO), according to practice-changing results of a new multicenter study. Of 1,083 women with BRCA mutations followed for a median of 5.1 years after RRSO, 8 incident uterine cancers were found, including 5 serous and/or serous-like endometrial carcinomas, an aggressive subtype.

Perioperative risks can be reduced with use of minimally invasive surgical approaches, add 3 experts editorializing on the study results.

Shu CA, Pike MC, Jotwanti AR, et al. Uterine cancer after risk-reducing salpingo-oophorectomy without hysterectomy in women with BRCA mutations [published online ahead of print June 30, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2016.1820.

Leath CA, Huh WK, Alvarez RD. Drawing the line in risk-reducing gynecologic surgery in women with a BRCA mutation [editorial; published online ahead of print June 30, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2016.1773.


 

EXPERT COMMENTARY

Although RRSO is routinely recommended to decrease the risk of ovarian as well as breast cancer in women who harbor BRCA mutations, whether or not surgery should include hysterectomy has not been clear. Shu and colleagues prospectively evaluated the risk of uterine cancer in BRCA1 and BRCA2 mutation carriers who underwent RRSO without hysterectomy at 1 of 9 centers in the United States or the United Kingdom, comparing it with rates expected from national surveillance data.

Details of the study

Among 1,083 women (median age, 45.6 years at the time of RRSO; median follow-up, 5.1 years), 8 incident uterine cancers were observed (4.3 were expected; observed to expected [O:E] ratio, 1.9; P = .09). In an analysis stratified by tumor subtype, no elevated risk for endometrioid endometrial cancer or sarcoma was noted. Five serous and/or serous-like endometrial cancers were observed after RRSO. Four were found in BRCA1 carriers and 1 in a BRCA2 carrier, with the O:E ratio of 22.2 ( P<.001) for BRCA1 and 6.4 ( P = .15) for BRCA2 carriers.

Details of the accompanying editorial

Commenting on the study, Leath and colleagues noted that while the number of cases was small, the study demonstrated a link between the presence of BRCA mutations (particularly BRCA1 mutations) and a "small but not null risk of endometrial cancer." Many of these uterine cancers have a serous histology, a concern due to the likelihood of worse outcomes compared with the more common endometrioid variant.

The authors suggest that clinicians make patients with BRCA mutations undergoing RRSO aware of the potential risks and benefits of concomitant hysterectomy and work to make an individualized decision based on the limitations of available data. They state, "Perhaps it is time to consider that the line for risk-reducing gynecologic surgery in patients with BRCA mutations not stop at the ovaries and fallopian tubes. Thus, concomitant hysterectomy with RRSO, when performed with a minimally invasive surgical approach, particularly for women with a BRCA1 mutation, should be able to be performed with minimum morbidity and allow for use of estrogen-only hormone therapy after surgery, if needed."

WHAT THIS EVIDENCE MEANS FOR PRACTICE

Although adding hysterectomy to RRSO increases the perioperative risks, these risks should be attenuated by the use of minimally invasive surgical approaches. Women diagnosed with serous endometrial cancer have worse outcomes than those with the more common endometrioid endometrial tumors, even when they are diagnosed with early stage disease. Future risk of any uterine malignancy is essentially eliminated when hysterectomy is performed.

Risk-reducing gynecologic surgery in BRCA carriers is optimally performed prior to age 40, meaning that unless hormone therapy is used, severe menopausal symptoms likely will occur, and women are at elevated risk for osteoporosis and cardiovascular and neurodegenerative diseases. Given that hysterectomy allows estrogen (little or no impact 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 who provided an accompanying comment on the study that—provided a minimally invasive approach is used—we should encourage hysterectomy as part of risk-reducing surgery for women with BRCA mutations.
ANDREW M. KAUNITZ, MD

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