title: Exemestane: one part of the chemopreventive spectrum for ER-positive breast cancer.
abstract: Development of drugs to prevent breast cancer has focused largely on anti-estrogenic agents, leading to approval by the US FDA of two such agents for this purpose: tamoxifen and raloxifene. However, the uptake of these drugs by high-risk women and their primary care physicians has been limited, due in large part to a perceived unfavorable risk:benefit balance. The current focus is on aromatase inhibitors, which appear to have more acceptable side effects in addition to being more efficacious in reducing breast cancer risk in high-risk women. The placebo-controlled phase III MAP.3 trial tested the AI exemestane in high-risk women and documented a 65% relative reduction in total and a 73% reduction in ER-positive breast cancers in the intervention compared to the placebo group. Toxicities centered around musculoskeletal side effects, but in the relatively short 35-month median follow-up period, these did not impair quality-of-life. A bone study nested within MAP.3 demonstrated significant decreases in bone mineral density (BMD) and in structural parameters of bone quality. The strengths and weaknesses of preventive exemestane as evaluated in the MAP.3 trial are discussed as are relevant areas for future consideration: influence of obesity, alternative dosing, and biomarker use in phase III prevention trials of aromatase inhibitors.
authors.affiliation: Division of Cancer Prevention, Chemoprevention Agent Development Research Group,National Institutes of Health, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Dunn
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cazzaniga
authors.forename: Andrea
authors.initials: A
authors.lastname: DeCensi
mesh_terms: D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000517:prevention & control*; D006801:Humans; D011960:Receptors, Estrogen / Q000032:analysis
chemical_list: D000730:Androstadienes; D016588:Anticarcinogenic Agents; D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen; C056516:exemestane