Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study.
BACKGROUND
Early menarche and late menopause are important risk factors for breast cancer, but their effects on breast cancer risk in BRCA1 and BRCA2 carriers are unknown.


METHODS
We assessed breast cancer risk in a large series of 1,187 BRCA1 and 414 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study. Rate ratios were estimated using a weighted Cox-regression approach.


RESULTS
Breast cancer risk was not significantly related to age at menopause [hazard ratio [HR] for menopause below age 35 years, 0.60 [95% confidence interval (95% CI), 0.25-1.44]; 35 to 40 years, 1.15 [0.65-2.04]; 45 to 54 years, 1.02 [0.65-1.60]; >or=55 years, 1.12 [0.12-5.02], as compared with premenopausal women]. However, there was some suggestion of a reduction in risk after menopause in BRCA2 carriers. There was some evidence of a protective effect of oophorectomy (HR, 0.56; 95% CI, 0.29-1.09) and a significant trend of decreasing risk with increasing time since oophorectomy, but no apparent effect of natural menopause. There was no association between age at menarche and breast cancer risk, nor any apparent association with the estimated total duration of breast mitotic activity.


CONCLUSIONS
These results are consistent with other observations suggesting a protective effect of oophorectomy, similar in relative effect to that in the general population. The absence of an effect of age at natural menopause is, however, not consistent with findings in the general population and may reflect the different natural history of the disease in carriers.
Chang-Claude
Jenny
J
Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280 69120 Heidelberg, Germany. j.chang-claude@dkfz-heidelberg.de
Andrieu
Nadine
N
Rookus
Matti
M
Brohet
Richard
R
Antoniou
Antonis C
AC
Peock
Susan
S
Davidson
Rosemarie
R
Izatt
Louise
L
Cole
Trevor
T
Noguès
Catherine
C
Luporsi
Elisabeth
E
Huiart
Laetitia
L
Hoogerbrugge
Nicoline
N
Van Leeuwen
Flora E
FE
Osorio
Ana
A
Eyfjord
Jorunn
J
Radice
Paolo
P
Goldgar
David E
DE
Easton
Douglas F
DF
D000328:Adult; D000367:Age Factors; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D015331:Cohort Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008572:Menarche / Q000502:physiology*; D008593:Menopause / Q000502:physiology*; D008875:Middle Aged; D009154:Mutation; D016016:Proportional Hazards Models; D012307:Risk Factors