Pharmacological prevention of breast cancer: quo vadis?

Although tamoxifen reduces breast cancer incidence by 30-40% in at-risk subjects, its adverse events may be a limiting factor. Thus, different strategies are being pursued to improve the risk:benefit ratio of breast cancer chemoprevention intervention. Firstly, raloxifene is being compared with tamoxifen in a phase-III trial, whereas the minimal active dose of tamoxifen is being assessed in phase I-II trials. The combination of HRT and tamoxifen may also reduce the risks while retaining the benefits of either agent. Anastrozole holds promise as a preventive agent based on preliminary data on contralateral breast cancer. Another important area is the appropriate identification of women at increased risk for ER-positive breast cancer due to reproductive factors, which may maximize the therapeutic index of hormonal agents. Finally, new targets that interfere with the onset of ER-negative breast cancer are being sought since one-third of breast cancers will not be modulated by hormonal interventions.