Aromatase inhibitors in breast cancer: from metastatic disease to adjuvant treatment

Abstract

Hormone management plays an important role in the treatment of women with breast cancer. In recent years, aromatase inhibitors have represented a step forward in the treatment of postmenopausal patients with advanced disease. Aromatase converts androgens in estradiol and estrone. In premenopausal woman, most of the produced estrogens come from the ovaries. After ovarian failure, the adrenal glands become the chief source of androgens, which are converted to estrogens by aromatase, in peripheral tissues like fat, skeletal muscle, liver, and the breast tumor itself. Thus, the inhibition of aromatase is a rationally designed strategy of proven efficacy, for decreasing circulating levels of estrogen in postmenopausal women. First- and second-generation aromatase inhibitors compared unfavorably with tamoxifen, either because of inferior efficacy, or due to increased toxicity. In addition to its antiestrogenic actions, tamoxifen has estrogenic properties that lead to side effects such as thromboembolic events and endometrial proliferation. In this paper, we discuss recent studies of the thirdgeneration aromatase inhibitors, which have been shown to be superior to megestrol acetate as the second-line treatment of advanced breast cancer. Further more, these drugs have been promising as first-line therapy, as well as in the neoadjuvant and adjuvant treatment.