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Risk factors for endometrial cancer among women with a BRCA1 or BRCA2 mutation: a case control study.

Abstract
BRCA mutation carriers may use tamoxifen for breast cancer prevention or treatment. Hormone replacement therapy is often prescribed after surgical menopause and oral contraceptives are recommended for ovarian cancer prevention. The objective of this study was to assess the impact of these medications and other risk factors on endometrial cancer risk in BRCA carriers. Women with a BRCA1 or BRCA2 mutation were identified from a registry of mutation carriers. Cases were 83 women who had a diagnosis of endometrial cancer. Controls were 1027 matched women who did not develop endometrial cancer and who had an intact uterus. All women completed a baseline questionnaire, which included questions about ages at menarche and menopause, oral contraceptive use, hormone replacement therapy use, hysterectomy, oophorectomy, breast cancer history and tamoxifen use. We estimated the odds ratio associated with each risk factor in a multivariate analysis. No differences were found between cases and controls in terms of age at menarche, BMI, smoking, or oral contraceptive use. In a multivariate analysis, for women taking estrogen-only hormone replacement therapy, the odds ratio was 0.23 (95% CI 0.03-1.78, p = 0.16), and for women taking progesterone-only hormone replacement therapy the odds ratio was 6.91 (95% CI 0.99-98.1, p = 0.05). The adjusted odds ratio for endometrial cancer associated with a history of tamoxifen use was 3.50 (95% CI 1.51-8.10, p = 0.003). The observed increased risk of endometrial cancer associated with progesterone-only therapy merits further study.
AuthorsYakir Segev, Barry Rosen, Jan Lubinski, Jacek Gronwald, Henry T Lynch, Pal Moller, Charmaine Kim-Sing, Parviz Ghadirian, Beth Karlan, Charis Eng, Dawna Gilchrist, Susan L Neuhausen, Andrea Eisen, Eitan Friedman, David Euhus, Sun Ping, Steven A Narod, Hereditary Breast Cancer Study Group
JournalFamilial cancer (Fam Cancer) Vol. 14 Issue 3 Pg. 383-91 (Sep 2015) ISSN: 1573-7292 [Electronic] Netherlands
PMID25838159 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Tamoxifen
Topics
  • Adult
  • Aged
  • BRCA1 Protein (genetics)
  • BRCA2 Protein (genetics)
  • Case-Control Studies
  • Endometrial Neoplasms (genetics, prevention & control)
  • Estrogen Replacement Therapy (methods)
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Hysterectomy
  • Middle Aged
  • Mutation
  • Odds Ratio
  • Ovariectomy
  • Risk Factors
  • Tamoxifen (therapeutic use)

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