Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group.
OBJECTIVE
Bilateral prophylactic oophorectomy (BPO) is widely used for cancer risk reduction in women with BRCA1/2 mutations. Many premenopausal women choose to take hormone replacement therapy (HRT) after undergoing BPO to abrogate immediate symptoms of surgically-induced menopause. Thus, we evaluated whether the breast cancer risk reduction conferred by BPO in BRCA1/2 mutation carriers is altered by use of post-BPO HRT.


METHODS
We identified a prospective cohort of 462 women with disease-associated germline BRCA1/2 mutations at 13 medical centers to evaluate breast cancer risk after BPO with and without HRT. We determined the incidence of breast cancer in 155 women who had undergone BPO and in 307 women who had not undergone BPO on whom we had complete information on HRT use. Postoperative follow-up was 3.6 years.


RESULTS
Consistent with previous reports, BPO was significantly associated with breast cancer risk reduction overall (hazard ratio [HR] = 0.40; 95%CI, 0.18 to 0.92). Using mutation carriers without BPO or HRT as the referent group, HRT of any type after BPO did not significantly alter the reduction in breast cancer risk associated with BPO (HR = 0.37; 95% CI, 0.14 to 0.96).


CONCLUSIONS
Short-term HRT use does not negate the protective effect of BPO on subsequent breast cancer risk in BRCA1/2 mutation carriers.
Rebbeck
Timothy R
TR
Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania School of Medicine, Philadelphia, 19104, USA. trebbeck@cceb.med.upenn.edu
Friebel
Tara
T
Wagner
Theresa
T
Lynch
Henry T
HT
Garber
Judy E
JE
Daly
Mary B
MB
Isaacs
Claudine
C
Olopade
Olufunmilayo I
OI
Neuhausen
Susan L
SL
van 't Veer
Laura
L
Eeles
Rosalind
R
Evans
D Gareth
DG
Tomlinson
Gail
G
Matloff
Ellen
E
Narod
Steven A
SA
Eisen
Andrea
A
Domchek
Susan
S
Armstrong
Katrina
K
Weber
Barbara L
BL
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D020249:Hormone Replacement Therapy; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D010052:Ovariectomy; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome