Although BRCA mutations confer increased risk for ovarian, fallopian tube, and primary peritoneal cancer, there have been limited and conflicting risks reported for endometrial cancer. Consequently, current practice guidelines only recommend the removal of the fallopian tubes and ovaries as a risk-reducing option for BRCA carriers.1 Specifically, through a prospective study of 4500 women with a BRCA mutation, there were 17 women identified with endometrial cancers (13 in BRCA1 and 4 in BRCA2) with an average follow-up time of 5.7 years.2 This suggested an overall endometrial cancer risk of 2-fold; although risks were higher (~4-fold) in those who received tamoxifen. The incidence of endometrial cancer was 2% at 10-years among those treated with tamoxifen. A subsequent study by the same group suggested the increased endometrial cancer risks among those with a history of tamoxifen use was associated with progesterone-only hormone replacement therapy, which warrants further study.3 These findings suggest that tamoxifen contributed substantially to the endometrial cancers seen among BRCA1 mutation carriers, although the actual risk is still fairly small. Consequently, in those considering tamoxifen, it may be important to discuss hysterectomy at the time of risk-reducing salpingo-oophorectomy (RRSO).
More recently, a prospective study of almost 1,100 BRCA carriers who had previously undergone removal of their tubes and ovaries, demonstrated an increased risk in BRCA1 carriers for a type of endometrial cancer called serous/serous-like. In this study, 8 women with endometrial cancer (of which 5 were serous/serous-like) were identified over an average follow-up time of 5.1 years.4 This suggested an overall elevation in endometrial cancer risk of almost 2-fold. The association of serous/serous-like endometrial cancer is particularly relevant as it only accounts for approximately 10% of endometrial cancer cases in the general population and is typically associated with aggressive disease and poor prognosis. As eloquently reviewed in the Leath et al editorial for this article,5 the risk of serous endometrial cancer among BRCA1 carriers may warrant a discussion of the potential risks and benefits of hysterectomy at the time of RRSO as well as a discussion about the limitations of our current knowledge in order for patients to make an individualized decision. In fact, a recent report of cancer risks among relatives of over 1000 BRCA mutation carriers detected no increased risk of endometrial cancer,6 highlighting the limited (if any) elevation of endometrial cancer risk. Taken together, these findings emphasize the need for further studies to refine risks and determine the need for hysterectomy both at time of RRSO as well as the role (if any) of risk-reducing hysterectomy among those who have already had an RRSO (as the risk of a second surgery may be greater than the risk of endometrial cancer).
1National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Genetic Familial High-Risk Assessment: Breast and Ovarian. Version 1.2016. Retrieved from: www.nccn.org.
2Segev Y, et al. Gynecol Oncol. 2013 Jul;130(1):127-31. PMID: 23562522.
3Segev Y, et al. Fam Cancer. 2015 Sep;14(3):383-91. PMID: 25838159.
4Shu CA, et al. JAMA Oncol. 2016 Jun 30. PMID: 27367496.
5Leath CA, et al. JAMA Oncol. 2016 Jun 30. PMID: 27367041.
6Streff H, et al. Oncologist. 2016 Jul;21(7):869-74. PMID: 27306910.