Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study.
OBJECTIVE
Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers.


METHODS
A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model.


RESULTS
During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance.


CONCLUSIONS
The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.
Kauff
Noah D
ND
Clinical Genetics and Gynecology Services, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 192, New York, NY 10021, USA. kauffn@mskcc.org
Domchek
Susan M
SM
Friebel
Tara M
TM
Robson
Mark E
ME
Lee
Johanna
J
Garber
Judy E
JE
Isaacs
Claudine
C
Evans
D Gareth
DG
Lynch
Henry
H
Eeles
Rosalind A
RA
Neuhausen
Susan L
SL
Daly
Mary B
MB
Matloff
Ellen
E
Blum
Joanne L
JL
Sabbatini
Paul
P
Barakat
Richard R
RR
Hudis
Clifford
C
Norton
Larry
L
Offit
Kenneth
K
Rebbeck
Timothy R
TR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000517:prevention & control*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000517:prevention & control*; D010052:Ovariectomy; D011446:Prospective Studies; D012307:Risk Factors; D040242:Risk Reduction Behavior; D012489:Salpingostomy