A critical need for molecular markers of breast cancer risk and risk reduction

Excerpt

Carcinogenesis is a chronic disease process underlying the clonal evolution of cells progressing to the point of uncontrolled growth, metastatic potential, and molecular heterogeneity. By convention, chemoprevention drugs are developed from a molecular perspective with the goal of interrupting carcinogenesis before the occurrence of invasive lesions or extreme heterogeneity. The most successful demonstration of cancer chemoprevention to date has been an overall 49% reduction of invasive breast cancer, with a similar reduction in premalignant lesions by tamoxifen in the Breast Cancer Prevention Trial (BCPT) [1]. It is noteworthy that the main effect of tamoxifen is likely to be mediated through the estrogen receptor (ER), as reflected by a 70% reduction of lesions that are ER-positive in contrast to little or no effect on the incidence of ER-negative lesions. For interventions that are related to ER as a target, a number of drug development issues remain to be addressed including dose, schedule, and the comparative net clinical benefit of various selective ER modulators versus pure anti-estrogens, aromatase inhibitors, and combinations. In the BCPT there were 13,388 participants, and there were more than 22,000 in the STAR trial. The large sample size that may be needed for a randomized clinical trial to observe a prevention effect severely limits the opportunity to explore a multiplicity of important questions in clinical chemoprevention. …