Background: The association between bone mineral density and breast cancer was investigated in a nested case-control study, involving 30 breast cancer cases and 120 controls, aged 68+/-6 (mean +/-S.D.) years, as part of the Dubbo Osteoporosis Epidemiology Study (Australia).

Methods: Bone mineral density (BMD, g/cm(2)) at the femoral neck and lumbar spine was measured by dual energy X-ray absorptiometry. Anthropometric data and reproductive history were collected by direct interview using a structured questionnaire.

Results: In univariate conditional logistic regression analysis, lower age at menarche, longer overall duration of lifetime ovulation and higher bone density were associated with higher risk of breast cancer. Among the breast cancer cases, 20% of subjects had lumbar spine BMD greater than 1.20 g/cm(2) (or 2.5 S.D. above the mean) compared with less than 1% of the controls. After adjusting for the effects of duration of lifetime ovulation and body mass index, each 0.1 g/cm(2) increase in lumbar spine and femoral neck BMD was associated with a 2.1-fold (95% CI: 1.3-3.4) and 1.5-fold (1.0-2.4) respectively, higher risk of breast cancer. Further adjustment for age at menarche, hormone replacement therapy, and parity did not alter the result. Thus, postmenopausal BMD, which is affected by lifetime exposure to estrogen, is also related to risk of breast cancer. Importantly, it is estimated that estrogen therapy in osteoporotic women, even if raising the risk of breast cancer by 70% as suggested by some studies, would not elevate their risk to the level experienced by their non-osteoporotic counterparts.

Conclusion: While the mechanism of this relationship remains to be explored, these data support the concept that lifetime exposure to estrogen is an indicator of risk of both breast cancer and osteoporosis. However, the use of estrogen in osteoporosis treatment would not elevate the risk of breast cancer in osteoporotic women up to the level experienced by their non-osteoporotic counterparts.