Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer.
OBJECTIVE
We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls.


METHODS
A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls.


RESULTS
There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05).


CONCLUSIONS
IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.
Pierce
Lori J
LJ
Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI 48109-0010, USA. ljpierce@umich.edu
Levin
Albert M
AM
Rebbeck
Timothy R
TR
Ben-David
Merav A
MA
Friedman
Eitan
E
Solin
Lawrence J
LJ
Harris
Eleanor E
EE
Gaffney
David K
DK
Haffty
Bruce G
BG
Dawson
Laura A
LA
Narod
Steven A
SA
Olivotto
Ivo A
IA
Eisen
Andrea
A
Whelan
Timothy J
TJ
Olopade
Olufunmilayo I
OI
Isaacs
Claudine
C
Merajver
Sofia D
SD
Wong
Julia S
JS
Garber
Judy E
JE
Weber
Barbara L
BL
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007557:Israel / Q000453:epidemiology; D015412:Mastectomy, Segmental; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D009367:Neoplasm Staging; D016017:Odds Ratio; D010052:Ovariectomy; D011237:Predictive Value of Tests; D018714:Radiotherapy, Adjuvant; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology