Aromatase inhibitors and their future role in post-menopausal women with early breast cancer

Abstract

Summary Anastrozole is the first aromatase inhibitor to show a significant survival advantage over megestrol acetate in post-menopausal women with advanced breast cancer. The rationale for extending the use of aromatase inhibitors to the treatment of early breast cancer is based on the efficacy observed in the advanced setting, combined with good tolerability and a convenient dosing regimen. Furthermore, oestrogen deprivation by ovarian ablation (similar to oestrogen antagonism with tamoxifen) is already established as an effective adjuvant treatment in premenopausal women with modality breast cancer. Anastrozole produces a profound suppression of plasma oestrogen levels which is greater than that obtained with earlier aromatase inhibitors (formestane, aminoglutethimide) or megestrol acetate. This could account for the differences in clinical efficacy seen between anastrozole and megestrol acetate. In terms of benefits over other endocrine agents, anastrozole causes significantly less weight gain than megestrol acetate; it does not have the partial agonist activity of tamoxifen, and is unlikely to lead to tumour stimulation in patients resistant to tamoxifen or to exert proliferative effects on the endometrium. The lack of oestrogen agonist activity, however, may possibly have detrimental effects on bone mineral density and blood lipid profile. Current clinical trials are investigating the efficacy and safety of anastrozole in the early breast cancer setting. The results of these trials will help to determine whether anastrozole has any benefits over tamoxifen, the current treatment of choice in post-menopausal women with early breast cancer.

TFF3 is a valuable predictive biomarker of endocrine response in metastatic breast cancer

“…Two main categories of drugs target the dependence of malignant breast epithelial cells upon oestrogens. Aromatase inhibitors inhibit cytochrome P450 CYP-19, the enzyme that converts androgens to oestrogens, and thereby reduce circulating concentrations of tumour-promoting oestrogens ( Lonning 1998 , Santen et al . 2009 ).…”

Randomized controlled trial comparing superovulation with letrozole versus recombinant follicle-stimulating hormone combined with intrauterine insemination for couples with unexplained infertility who had failed clomiphene citrate stimulation and intrauterine insemination

“…Letrozole, as well as anastrozole, are competitive aromatase inhibitors with high potency and rapidly reversible action (20,21). Letrozole is readily absorbed after oral administration and it is mainly cleared by the liver with a mean half-life of approximately 45 hours.…”

Management of Male Breast Cancer: The Journey so Far and Future Directions

“…Anastrozole, a selective AI, is one of the most used endocrine therapies for postmenopausal FBC [58][59][60][61]. Giordano et al reported that among five ER-positive MaBC who were treated with anastrozole, three patients showed disease stabilization and two showed marked improvement; however, none of the patients achieved complete response [62].…”