Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate. We undertook a prospective analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers.



Subjects had no history of cancer, had both breasts intact, and had information on oophorectomy status (n = 3722). Women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. A Cox regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with oophorectomy (coded as a time-dependent variable). All statistical tests were two-sided.



Over a mean follow-up of 5.6 years, 350 new breast cancers were diagnosed. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy. The age-adjusted hazard ratio associated with oophorectomy was 0.96 (95% CI = 0.73 to 1.26, P = 76) for BRCA1 and was 0.65 (95% CI = 0.37 to 1.16, P = 14) for BRCA2 mutation carriers. In stratified analyses, the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years (age-adjusted HR = 0.18, 95% CI = 0.05 to 0.63, P = 007). Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers (age-adjusted HR = 0.79, 95% CI = 0.55 to 1.13, P = 51).



Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation.
Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
Joanne
J
Kotsopoulos
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Tomasz
T
Huzarski
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Jacek
J
Gronwald
Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Christian F
CF
Singer
Department for Medical Genetics, Inherited Cancer Research Group, and Department of Tumor Biology, Institute of Cancer Research, Norwegian Radium Hospital; Oslo University Hospital, Oslo, Norway.
Pal
P
Moller
Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE.
Henry T
HT
Lynch
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, ON, Canada.
Susan
S
Armel
Gynecology Oncology, Cedars Sinai Medical Center, Los Angeles, CA.
Beth
B
Karlan
Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, QC, Canada.
William D
WD
Foulkes
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA.
Susan L
SL
Neuhausen
Division of Human Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH.
Leigha
L
Senter
Beth Israel Deaconess Medical Center, Boston, MA.
Nadine
N
Tung
City of Hope National Medical Center, Duarte, CA.
Jeffrey N
JN
Weitzel
Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada.
Andrea
A
Eisen
Faculty of Nursing, University of Toronto, ON, Canada.
Kelly
K
Metcalfe
Genomic Medicine Institute and Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, OH.
Charis
C
Eng
Moffitt Cancer Center, Departments of Cancer Epidemiology, Biostatistics, Anatomic Pathology, and Experimental Therapeutics, Tampa, FL.
Tuya
T
Pal
Genomic Medicine, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK (GE).
Gareth
G
Evans
Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
Ping
P
Sun
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Jan
J
Lubinski
Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
Steven A
SA
Narod
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009154:Mutation; D010052:Ovariectomy; D065286:Prophylactic Surgical Procedures; D011446:Prospective Studies; D055815:Young Adult