Aromatase inhibitors and inactivators for breast cancer therapy

Abstract

Aromatase inhibitors and inactivators are increasingly important to the therapy of advanced breast cancer in postmenopausal women. These compounds are also currently being evaluated in the adjuvant setting and may have potential in breast cancer prevention. In addition to the recent clinical results, experimental research with development of aromatase 'knockout' mice as well as certain clinical observations in individuals lacking this enzyme have deepened our understanding of estrogens outside of the field of reproduction. Such information should help us to further develop this type of therapy in breast cancer and, in particular, extend our understanding of the lack of complete cross-resistance between aromatase inhibitors and inactivators. Clinically, third-generation aromatase inhibitors and inactivators have shown superiority compared with conventional treatment in advanced postmenopausal breast cancer with respect to second-line (tamoxifen failures) as well as first-line therapy. The fact that tamoxifen is noncurative in metastatic disease but improves long-term survival in the adjuvant setting suggests that even modest improvements in therapy of advanced disease may be translated into survival benefits in patients with early disease. In addition, these novel compounds with lack of complete cross-resistance extend the scope of using sequential treatment options to maximise the duration of optimal endocrine therapy in metastatic breast cancer disease.