Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group.
OBJECTIVE
Data on the efficacy of bilateral prophylactic mastectomy for breast cancer risk reduction in women with BRCA1 and BRCA2 (BRCA1/2) mutations are limited, despite the clinical use of this risk-management strategy. Thus, we estimated the degree of breast cancer risk reduction after surgery in women who carry these mutations.


METHODS
Four hundred eighty-three women with disease-associated germline BRCA1/2 mutations were studied for the occurrence of breast cancer. Cases were mutation carriers who underwent bilateral prophylactic mastectomy and who were followed prospectively from the time of their center ascertainment and their surgery, with analyses performed for both follow-up periods. Controls were BRCA1/2 mutation carriers with no history of bilateral prophylactic mastectomy matched to cases on gene, center, and year of birth. Both cases and controls were excluded for previous or concurrent diagnosis of breast cancer. Analyses were adjusted for duration of endogenous ovarian hormone exposure, including age at bilateral prophylactic oophorectomy if applicable.


RESULTS
Breast cancer was diagnosed in two (1.9%) of 105 women who had bilateral prophylactic mastectomy and in 184 (48.7%) of 378 matched controls who did not have the procedure, with a mean follow-up of 6.4 years. Bilateral prophylactic mastectomy reduced the risk of breast cancer by approximately 95% in women with prior or concurrent bilateral prophylactic oophorectomy and by approximately 90% in women with intact ovaries.


CONCLUSIONS
Bilateral prophylactic mastectomy reduces the risk of breast cancer in women with BRCA1/2 mutations by approximately 90%.
Center for Clinical Epidemiology and Biostatistics, Abramson Family Cancer Research Institute, The University of Pennsylvania, Philadelphia, PA 19104-6021, USA.
Timothy R
TR
Rebbeck
Tara
T
Friebel
Henry T
HT
Lynch
Susan L
SL
Neuhausen
Laura
L
van 't Veer
Judy E
JE
Garber
Gareth R
GR
Evans
Steven A
SA
Narod
Claudine
C
Isaacs
Ellen
E
Matloff
Mary B
MB
Daly
Olufunmilayo I
OI
Olopade
Barbara L
BL
Weber
D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D016022:Case-Control Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D009154:Mutation; D009656:North America / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012189:Retrospective Studies; D018570:Risk Assessment; D016896:Treatment Outcome