Antiaromatase agents: preclinical data and neoadjuvant therapy.

Novel drugs such as exemestane are highly potent and specific inactivators of aromatase activity in test systems such as placental microsomes, breast cancer homogenates, and cultures of mammary fibroblasts, with IC50 values in the nmol range. When given in daily milligram amounts to postmenopausal women, exemestane almost totally blocks peripheral aromatase and reduces circulating estrogens to levels that are at the limit of detection of current assays. Additionally, exemestane profoundly inhibits in situ aromatase activity both in breast cancers and surrounding nonmalignant breast. In postmenopausal women with large estrogen receptor-rich cancers, these endocrine influences translate into antitumor effects, and, for example, following exemestane treatment in the neoadjuvant setting, tumor resolution may be observed on mammography. In conclusion, the ability to block estrogen biosynthesis peripherally and locally within the breast provides new options for the treatment of hormone-sensitive breast cancers in postmenopausal women