Risk factors for breast cancer in older women: the relative contribution of bone mineral density and other established risk factors

Aim To determine the contribution of bone mineral density (BMD) to breast cancer risk relative to other established breast cancer risk factors in postmenopausal women with osteoporosis. Methods Data for this analysis comprised those collected from women randomized to placebo in the MORE and CORE trials ( N = 2,576). Risk factors measured at baseline included age, family history of breast cancer, estradiol level, body mass index, prior hormone therapy, BMD and vertebral fracture status. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results Over a total of 13,698 woman-years of follow-up, 65 incident breast cancers occurred. In univariate analyses, older age and family history of breast cancer were the strongest predictors of breast cancer risk, associated with a 2.4- and 2.6-fold increase in breast cancer incidence. A higher estradiol level was associated with a 1.9-fold increase in breast cancer incidence. The association between femoral neck BMD and breast cancer incidence was only significant after adjustment for age ( P = 0.03). The final multivariable model included age, family history, estradiol, BMD, and the BMD-estradiol interaction since the effect of BMD on breast cancer varied by estradiol level (interaction P -value, 0.04); in those with a lower estradiol level, a higher BMD was associated with a 2.6-fold increased in breast cancer. Conclusion Overall, BMD is a relatively weak predictor of breast cancer risk in these postmenopausal women with osteoporosis, after taking into consideration age, family history and endogenous estradiol level.