title: Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations.
abstract: OBJECTIVE
  The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial.
  
  
  OBJECTIVE
  To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy.
  
  
  METHODS
  This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression.
  
  
  METHODS
  Incidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database.
  
  
  RESULTS
  Among the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1-56.9; P < .001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2-35.5; P = .15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors.
  
  
  CONCLUSIONS
  Although the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women.
authors.affiliation: Division of Hematology-Oncology, Columbia University Medical Center, New York, New York.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Shu
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
authors.affiliation: Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Anjali R
authors.initials: AR
authors.lastname: Jotwani
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Friebel
authors.affiliation: Gynecologic Pathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.affiliation: Basser Center for BRCA and Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Nathanson
authors.affiliation: Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Konner
authors.affiliation: Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Angela G
authors.initials: AG
authors.lastname: Arnold
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Faina
authors.initials: F
authors.lastname: Bogomolniy
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Fanny
authors.initials: F
authors.lastname: Dao
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Narciso
authors.initials: N
authors.lastname: Olvera
authors.affiliation: Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust, London, England.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Bancroft
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Goldfrank
authors.affiliation: Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Zsofia K
authors.initials: ZK
authors.lastname: Stadler
authors.affiliation: Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York10Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Robson
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Brown
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Mario M
authors.initials: MM
authors.lastname: Leitao
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Nadeem R
authors.initials: NR
authors.lastname: Abu-Rustum
authors.affiliation: Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Aghajanian
authors.affiliation: Baylor-Charles A. Sammons Cancer Center, Texas Oncology, Dallas.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Blum
authors.affiliation: Department of Population Sciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.affiliation: Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Daly
authors.affiliation: Department of Oncology and Medicine, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC.
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.affiliation: Institute of Cancer Research, Royal Marsden National Health Service Foundation Trust, London, England.
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
authors.affiliation: UCLA Schools of Public Health and Medicine, University of California, Los Angeles16Center for Cancer Prevention and Control Research, University of California, Los Angeles17Jonsson Comprehensive Cancer Center, University of California, Los Angeles.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.affiliation: Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Barakat
authors.affiliation: Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.affiliation: Basser Center for BRCA and Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.affiliation: Clinical Cancer Genetics Program, Duke Cancer Institute, Duke University Health System, Durham, North Carolina.
authors.forename: Noah D
authors.initials: ND
authors.lastname: Kauff
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007044:Hysterectomy; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009154:Mutation; D010052:Ovariectomy; D011446:Prospective Studies; D012306:Risk; D058994:Salpingectomy; D014594:Uterine Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control*