The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations: An international prospective cohort study

Yakir Segev, Javaid Iqbal, Jan Lubinski, Jacek Gronwald, Henry T. Lynch, Pal Moller, Parviz Ghadirian, Barry Rosen, Nadine Tung, Charmaine Kim-Sing, William D. Foulkes, Susan L. Neuhausen, Leigha Senter, Christian F. Singer, Beth Karlan, Sun Ping, Steven A. Narod

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Abstract

Objective To evaluate the risk of endometrial cancer in women who carry a mutation in the BRCA1 or the BRCA2 gene. Methods We followed 4456 women with a BRCA1 or a BRCA2 mutation for incident cases of endometrial cancer. The incidence of endometrial cancer was estimated per 100,000 women per year. The hazard ratios for endometrial cancer were estimated by calculating standardized incidence ratios (SIRs) according to age group and country of residence. We estimated the impact of tamoxifen and hormone replacement therapy on the incidence of endometrial cancer in BRCA1 and BRCA2 carriers. Results After a mean follow-up of 5.7 years, we identified 17 endometrial cancers (13 cases in BRCA1 and 4 cases in BRCA2). The SIR for BRCA1 carriers was 1.91 (95% CI: 1.06-3.19, p = 0.03) and for BRCA2 carriers was 1.75 (95% CI: 0.55-4.23, p = 0.2). The SIR was 4.14 (95% CI: 1.92 to 7.87) for women who received tamoxifen and was 1.67 (95% CI: 0.81 to 3.07) for women who did not receive tamoxifen. The ten-year cumulative risk of endometrial cancer in women who were treated with tamoxifen was 2.0%. Conclusions The risk of endometrial cancer is higher in BRCA1 mutation carriers than in the general population. The excessive risk is largely attributable to a history of tamoxifen use, but the actual risk of endometrial cancer associated with tamoxifen is small. It is important to discuss hysterectomy at the time of prophylactic bilateral salpingo-oophorectomy if tamoxifen is to be considered.

Original languageEnglish (US)
Pages (from-to)127-131
Number of pages5
JournalGynecologic Oncology
Volume130
Issue number1
DOIs
StatePublished - Jul 1 2013

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynecology

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    Segev, Y., Iqbal, J., Lubinski, J., Gronwald, J., Lynch, H. T., Moller, P., Ghadirian, P., Rosen, B., Tung, N., Kim-Sing, C., Foulkes, W. D., Neuhausen, S. L., Senter, L., Singer, C. F., Karlan, B., Ping, S., & Narod, S. A. (2013). The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations: An international prospective cohort study. Gynecologic Oncology, 130(1), 127-131. https://doi.org/10.1016/j.ygyno.2013.03.027