Age at menarche, age at menopause, height and obesity as risk factors for breast cancer: associations and interactions in an international case-control study.

The importance of age at menarche, age at menopause, height, and obesity as risk factors for breast cancer, and the possible interactions among these factors in breast cancer causation were investigated in a data set collected in the late 1960's, in an international multicenter case-control study. Multiple logistic regression procedures were used to model data from 3,993 breast cancer cases and 11,783 controls from 7 study centers representing the range of international variation of breast cancer incidence. Height and obesity (measured through the weight/height2 index) were independent risk factors for breast cancer among post-menopausal but not pre-menopausal women; post-menopausal women taller by 10 cm had a 12% higher risk of breast cancer (95% confidence interval, CI, 3-21%) and post-menopausal women of average height (say 158 cm) had an 11% higher risk of breast cancer (CI 7-16%) when they were heavier by 10 kg (and, therefore, more obese by 4 kg/m2). Age at menarche was a risk factor among both pre-menopausal and post-menopausal women, a delay of 2 years corresponding to a 10% reduction in breast cancer risk (CI 6-15%). Age at menopause was also a breast cancer risk factor, women with menopause at each 5 year age difference having a 17% higher risk of breast cancer (CI 11-22%). There is evidence of an interaction (deviation from the logistic regression-postulated multiplicativity) between obesity and age at menarche, implying that the protective effect of late menarche may not apply to overweight women or that late menarche may become detrimental in obese women. The estimated relative risk coefficients, when applied to average risk factor levels observed among control women, can explain only a small fraction of the difference in breast cancer incidence between Boston and Tokyo.