Retinoids and breast cancer prevention.

Abstract

Preclinical models suggest that retinoids inhibit mammary carcinogenesis. Induction of apoptosis is a unique feature of fenretinide, the most studied retinoid in clinical trials of breast cancer chemoprevention due to its selective accumulation in breast tissue and its favorable toxicological profile. In a phase III breast cancer prevention trial, fenretinide showed a very strong trend of reduction of incidence of second breast malignancies in premenopausal women, which was confirmed by the 15-year follow-up. Interestingly, ovarian cancer incidence appeared reduced during treatment in the same trial. This warrants further research on fenretinide mechanisms of action and potential efficacy and provides the rationale for a phase III primary prevention trial in young women at high risk for breast cancer.