Breast cancer is the major malignancy among women in the Western world. The breast is clearly a target organ for sex steroid hormones and hormonal treatments have been associated with an increased risk of breast cancer. The balance between proliferation and apoptosis is important for breast cell homeostasis. Mammographic breast density has been identified as a strong and independent risk factor for breast cancer. It seems clear that there is a difference between various hormonal treatments with regard to their effects on breast density and cell proliferation. Also, not all women respond similarly to the same treatment. Combined estrogen and progestogen therapy generally will enhance density and proliferation more than treatment with estrogen alone. Certain constitutional and hormonal factors appear to be predictive of breast reactivity. Older women with a low body mass index respond more strongly to treatment. Estrogen levels have a positive and androgens a negative association to increase in density and proliferation. A combination of increased proliferation and decreased apoptosis could be one mechanism to explain the excess risk of breast cancer during combined estrogen/progestogen treatment. Tibolone seems to have less impact on breast response than conventional hormone therapy.

Efforts should be made to identify those women with an adverse response to treatment as well as therapeutic principles with the least possible influence on the breast.