Aromatase inhibitors

Aromatase inhibitor
Drug class
Anastrozole, a nonsteroidal aromatase inhibitor and a widely used drug in the treatment of breast cancer.
Class identifiers
Synonyms	Estrogen synthesis inhibitors; Estrogen synthase inhibitors; Estrogen blockers
Use	Breast cancer, infertility, precocious puberty, medical abortion, gynecomastia, endometriosis, short stature, others
ATC code	L02BG
Biological target	Aromatase
Chemical class	Steroidal; Nonsteroidal

Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and gynecomastia in men. They may also be used off-label to reduce increase of estrogen conversion during cycle with external testosterone. They may also be used for chemoprevention in high risk women.

Aromatase is the enzyme that synthesizes estrogen. As breast and ovarian cancers require estrogen to grow, AIs are taken to either block the production of estrogen or block the action of estrogen on receptors.

In contrast to premenopausal women, in whom most of the estrogen is produced in the ovaries, in postmenopausal women estrogen is mainly produced in peripheral tissues of the body. Because some breast cancers respond to estrogen, lowering estrogen production at the site of the cancer (i.e. the adipose tissue of the breast) with aromatase inhibitors has been proven to be an effective treatment for hormone-sensitive breast cancer in postmenopausal women. Aromatase inhibitors are generally not used to treat breast cancer in premenopausal women. When aromatase inhibitors are used in premenopausal women, the decrease in estrogen activates the hypothalamus and pituitary axis to increase gonadotropin secretion, which in turn stimulates the ovary to increase androgen production. The heightened gonadotropin levels also upregulate the aromatase promoter, increasing aromatase production in the setting of increased androgen substrate. This counteracts the effect of the aromatase inhibitor in premenopausal women since total estrogen is increased. Ongoing areas of clinical research is optimizing adjuvant hormonal therapy in postmenopausal women with breast cancer. Although tamoxifen (SERM) had been the traditional drug treatment of choice, the ATAC trial has shown that clinical results are superior with an AI in postmenopausal women with localized breast cancer that is estrogen receptor positive. Trials of AIs in the adjuvant setting (given to prevent relapse after surgery for breast cancer) show that they are associated with a better disease-free survival than tamoxifen, but few conventionally-analyzed clinicals trials have shown that AIs have an overall survival advantage compared with tamoxifen, and there is no good evidence they are better tolerated.