Antihormones in prevention and treatment of breast cancer

Breast cancer has the highest incidence of all types of cancer in women. Age and family history are the strongest risk factors, but sex hormones also play an important role, as demonstrated by epidemiological studies reporting a consistent association by reproductive personal history and breast cancer risk. The acceptability of preventive strategies by healthy women is closely related to their lifetime risk of developing breast cancer. Although surgical prevention may be considered in carriers of BRCA1/2 mutation, this option cannot be advocated for the majority of women whose risk is only moderately increased. In these women, chemoprevention with tamoxifen may reduce the incidence of estrogen receptor (ER)-positive breast carcinoma by 30-50%. Other drugs such as raloxifen and aromatase inhibitors (AIs) are currently being tested in this setting. Tamoxifen has been the most successful hormonal treatment over the last 30 years and, until recently, the most active drug in endocrine-sensitive breast cancer. In premenopausal breast cancer, tamoxifen still represents the therapy of choice, alone or in association with ovarian suppression. Conversely, in postmenopausal women it has been overtaken by third-generation AIs as first-choice drugs both in the adjuvant and metastatic settings. Many other issues, such as the optimal sequence between tamoxifen and AIs, the duration of AIs treatment, and the association of ovarian suppression and AIa in premenopausal patients still await the completion of randomized clinical trials. Furthermore, it is likely that treatment tailoring will be increased by the definition of patient subgroups that could derive larger benefits from AIs (progesterone receptor-negative, HER-2-overexpressing) or other new drugs.