title: Effect of Oophorectomy on Survival After Breast Cancer in BRCA1 and BRCA2 Mutation Carriers.
abstract: OBJECTIVE
  Women who carry a germline mutation in either the BRCA1 or BRCA2 gene face a lifetime risk of breast cancer of up to 70%, and once they receive a diagnosis of breast cancer, they face high risks of both second primary breast and ovarian cancers. Preventive bilateral salpingo-oophorectomy is recommended to women with a BRCA mutation at age 35 years or thereafter to prevent breast and ovarian cancer, but it is unclear whether oophorectomy has an impact on survival in women with BRCA-associated breast cancer.
  
  
  OBJECTIVE
  To estimate the impact of oophorectomy on survival in women with breast cancer with a BRCA1 or BRCA2 mutation.
  
  
  METHODS
  Retrospective analysis of patients selected by pedigree review of families who received counseling at 1 of 12 participating clinical genetics centers. Patients were 676 women with stage I or II breast cancer and a BRCA1 or BRCA2 mutation who were observed for up to 20 years after receiving a diagnosis between 1975 and 2008. Survival experience was compared for women who did and who did not undergo oophorectomy.
  
  
  METHODS
  In all analyses, the primary end point was death due to breast cancer.
  
  
  RESULTS
  Of the 676 women, 345 underwent oophorectomy after the diagnosis of breast cancer and 331 retained both ovaries. The 20-year survival for the entire patient cohort was 77.4%. The adjusted hazard ratio for death attributed to breast cancer in women who underwent oophorectomy was 0.38 (95% CI, 0.19-0.77; P = .007) for BRCA1 carriers and 0.57 (95% CI, 0.23-1.43; P = .23) for BRCA2 carriers. The hazard ratio for breast cancer-specific mortality was 0.76 (95% CI, 0.32-1.78; P = .53) for women with estrogen receptor-positive breast cancer and 0.07 (95% CI, 0.01-0.51; P = .009) for women with estrogen receptor-negative breast cancer.
  
  
  CONCLUSIONS
  Oophorectomy is associated with a decrease in mortality in women with breast cancer and a BRCA1 mutation. Women with estrogen receptor-negative breast cancer and a BRCA1 mutation should undergo oophorectomy shortly after diagnosis.
authors.affiliation: Women's College Research Institute, Toronto, Ontario, Canada2Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kelly
authors.initials: K
authors.lastname: Metcalfe
authors.affiliation: Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska.
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.affiliation: Program in Cancer Genetics, McGill University, Montreal, Canada.
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Nadine
authors.initials: N
authors.lastname: Tung
authors.affiliation: British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Charmaine
authors.initials: C
authors.lastname: Kim-Sing
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.affiliation: Toronto Sunnybrook Regional Cancer Center, Toronto, Ontario, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Eisen
authors.affiliation: Department of Obstetrics and Gynecology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Barry
authors.initials: B
authors.lastname: Rosen
authors.affiliation: Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska.
authors.forename: Carrie
authors.initials: C
authors.lastname: Snyder
authors.affiliation: Women's College Research Institute, Toronto, Ontario, Canada2Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shelley
authors.initials: S
authors.lastname: Gershman
authors.affiliation: Women's College Research Institute, Toronto, Ontario, Canada.
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.affiliation: Women's College Research Institute, Toronto, Ontario, Canada.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002170:Canada; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D010052:Ovariectomy / Q000009:adverse effects / Q000401:mortality; D010641:Phenotype; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor