Letrozole is a nonsteroidal aromatase inhibitor that effectively blocks estrogen synthesis in postmenopausal women and is used as therapy of estrogen receptor-positive breast cancer, usually after surgical resection and after the failure of tamoxifen (Nolvadex, Soltamox). Letrozole is often given to women who have been taking tamoxifen for 5 years. Aromatase is the enzyme responsible for the conversion of testosterone to estrone (E1) and of androstenedione to estradiol (E2). The highest levels of aromatase are found in the ovary and placenta, which are the major sources of estrogen in premenopausal women. However, aromatase is also found in other tissues, such as the liver, kidney, adrenals, brain, muscle, and subcutaneous fat where it is also active in producing estrogens, although at low levels. These tissues are the major source of estrogen in postmenopausal women. Inhibitors of aromatase were developed to block the synthesis of estrogen in the peripheral tissues and, thus, as antiestrogen therapy of breast cancer in postmenopausal women. Letrozole is a nonsteroidal, specific aromatase inhibitor that has little or no effect on adrenal glucocorticoid or mineralocorticoid synthesis. Letrozole was approved for use in postmenopausal women with estrogen receptor-positive breast cancer in the United States in 1997. Current indications are as adjuvant therapy in postmenopausal women with estrogen-sensitive breast cancer, given in daily oral doses for up to five years. Letrozole is also indicated as a first-line treatment of estrogen receptor-positive (or unknown), locally advanced, or metastatic breast cancer in postmenopausal women.

Letrozole lowers estrogen levels in postmenopausal women, which may slow the growth of certain types of breast tumors that need estrogen to grow in the body.