BRCA mutations and risk of uterine cancer

Abstract

www.thelancet.com/oncology Vol 17 August 2016 e324 Women who carry the BRCA gene mutation that increases their risk of breast and ovarian cancers might also be at higher risk of developing an aggressive form of uterine cancer, suggests new research by Catherine Shu (Columbia University Medical Center, New York, NY, USA) and colleagues. Previous studies have identified a link between BRCA gene mutation and uterine cancer, but others have suggested that tamoxifen use is responsible for the increased risk of this cancer. For this study, coauthor Noah Kauff (Duke Cancer Institute, Durham, NC, USA) and international colleagues analysed data from 1083 women who had BRCA1 or BRCA2 mutations and had undergone risk-reducing salpingooophorectomy (RRSO) without a previous or concomitant hysterectomy. The overall risk of uterine corpus cancer (the main outcome) in women with BRCA mutations was not increased compared with the general population (eight uterine cancers reported during 6377 woman-years of follow-up; 4·3 expected, observed to expected [O:E] ratio 1·9 [95% CI 0·8–3·7], p=0·09). However, of those eight cancers, fi ve were of an aggressive uncommon subtype called serous or serous-like endometrial carcinoma, four in women with a BRCA1 mutation (0·18 expected, O:E ratio 22·2 [6·1–56·9], p<0·001) and one in a woman with a BRCA2 mutation (0·16 expected, O:E ratio 6·5 [0·2–35·5], p=0·15). The estimated risk for developing serous or serous-like carcinoma for women with BRCA1 undergoing RRSO at age 45 years through age 70 years was 2·6% (95% CI 0·7–6·8) assuming a constant annual risk, and 4·7% (1·3–12·1) assuming a constant relative risk. Kauff said, “The data show a small, but real risk of aggressive uterine cancer among women with BRCA1. It would make a great deal of sense for women to discuss the pros and cons of having a hysterectomy with their clinician, especially as serous endometrial cancer has a 50% mortality rate”. James Brenton (Cancer Research UK, London, UK) said, “These new fi ndings are potentially important for deciding the best strategy for carrying out preventive surgery for women who have BRCA1 and BRCA2 mutations, particularly if only the fallopian tubes are removed”. But Martin Widschwendter (University College London Institute for Women’s Health, London, UK), cautioned that other aspects should be investigated before recommending a hysterectomy, such as recommending weight loss and avoiding tamoxifen in favour of aromatase inhibitors.