Aromatase inhibitors in metastatic breast cancer

Inhibition of estrogen production or actions provides an effective therapy for patients with hormone-dependent breast cancer. A number of approaches to accomplishing these goals are available, and each has its own advantages and disadvantages. Aromatase inhibitors are capable of lowering estrogen levels in postmenopausal women whose estrogen production is not ovarian. Aromatase, the enzyme that converts androgens to estrogens, is one of a series of related P-450 enzymes involved in the production of steroid hormones. Because of the similarity of the P-450 enzymes, selectivity is important; nonselective aromatase inhibitors, such as aminoglutethimide, can affect enzymes controlling the production of other steroids and lead to significant side effects. Recently, a number of newer aromatase inhibitors have been synthesized and are in preclinical or clinical development. In early 1996, anastrozole became available for clinical use in the United States and in a number of other countries. In phase I studies, anastrozole was shown to be highly selective and inhibited estrogen production in postmenopausal patients to levels below the detection threshold of the assay. Another aromatase inhibitor in advanced development is fadrozole. In this review we present briefly the available clinical data on fadrozole and anastrozole.