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.