Phase 3 Trials in Breast Cancer Prevention: Focus on Estrogen-Targeting Agents, Selective Estrogen Receptor Modulators and Aromatase Inhibitors

Worldwide, breast cancer is the most common cancer in women, with 1.38 million breast cancer diagnoses cases estimated for 2008, accounting for 23% of all cancers in women. Breast cancer has the highest mortality rate of all cancers among women worldwide. Although technological advances in early detection and treatment have made inroads into these rates, breast cancer associated mortality remains high. Hence, interest has emerged in exploring approaches to preventing this disease and developing risk models to identify women most likely to benefit from preventive interventions. The current chapter addresses breast cancer risk-reducing agents that have progressed in their development to testing in phase III clinical trials or in some cases to formal approval for a breast cancer risk reduction indication. The discussion here concentrates on agents targeting estrogen receptor (ER)-positive breast cancers, specifically selective ER modulators (SERMs) and aromatase inhibitors (AIs). The large phase III clinical trials assessing efficacy of these agents in breast cancer prevention are the focus, as these represent the gold standard in clinical testing and serve as the basis for approval of these anti-estrogens for risk reduction of breast cancer among high-risk women.