title: The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations: an international prospective cohort study.
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.
authors.affiliation: Women's College Research Institute, Familial Breast Cancer Research, 790 Bay Street, Toronto, Ontario, M5G 1N8, Canada.
authors.forename: Yakir
authors.initials: Y
authors.lastname: Segev
authors.forename: Javaid
authors.initials: J
authors.lastname: Iqbal
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Pal
authors.initials: P
authors.lastname: Moller
authors.forename: Parviz
authors.initials: P
authors.lastname: Ghadirian
authors.forename: Barry
authors.initials: B
authors.lastname: Rosen
authors.forename: Nadine
authors.initials: N
authors.lastname: Tung
authors.forename: Charmaine
authors.initials: C
authors.lastname: Kim-Sing
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: Leigha
authors.initials: L
authors.lastname: Senter
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Beth
authors.initials: B
authors.lastname: Karlan
authors.forename: Sun
authors.initials: S
authors.lastname: Ping
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D016889:Endometrial Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000601:surgery; D005060:Europe / Q000453:epidemiology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D010052:Ovariectomy; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen