Aromatase Inhibitors DrugBank Online

These results contrast with those of the steroidal AI exemestane and tamoxifen, wherein the combination was more effective in reducing tumor growth than either agent alone in an experimental model (Figure 3) [64, 65]. A mechanism explaining the additive effects of the steroidal AI exemestane in combination with tamoxifen has not been established and warrants further evaluation. Although aromatase in normal tissues is differentially regulated through a variety of promoters [24], there appears to be only one human aromatase gene and a single protein translate. However, it is possible that in tumors there may be mutations that could affect aromatase protein structure or sensitivity to inhibitors. In this respect, structural functional studies on aromatase have produced proteins that appear resistant to a steroidal AI (formestane) while maintaining sensitivity to nonsteroidal AIs [25]. Such a phenotype has been reported in some breast cancers, for which causative mutations have not been identified [26].

What can I do to help recover from aromatase inhibitor therapy?

However, based on in vivo data, this occurs relatively quickly (i.e., within 1–2 days) [20]. In addition, the pharmacokinetic properties of each specific AI affect the duration of estrogen https://www.aaaecommerce.com/post-course-therapy-effects/ suppression. In any event, the clinical scheduling for exemestane, as with the nonsteroidal inhibitors, is daily dosing [6]. The inductive/stabilizing effects of nonsteroidal AIs on aromatase protein do not seem to affect their ability to lower estrogen levels or whole body aromatase activity in the short term [21, 22]. When given daily in therapeutic doses, both letrozole and anastrozole profoundly inhibit aromatase activity and effectively suppress estrogen levels in postmenopausal women at 3 months.

• However, a recent study using MCF-7aro cells made resistant to AIs indicates that differential patterns of gene expression are found according to different AIs, again suggesting that mechanisms of resistance are different [60, 61].
• Issues of endocrine effectiveness, safety, sequence, and combination treatment still remain.
• This review summarizes the available evidence regarding known differences and evaluates their potential clinical impact.
• For a summary of research studies on aromatase inhibitors and early breast cancer, visit the Breast Cancer Research Studies section.
• Hormone therapy works by either lowering the amount of hormones in the body or by blocking them from getting to breast cancer cells.
• In addition to pharmaceutical AIs, some natural elements have aromatase inhibiting effects, such as damiana leaves.

However, some premenopausal women may take an aromatase inhibitor when combined with ovarian suppression. Based on an initial finding that the first clinically used AI, aminoglutethimide, enhances tamoxifen clearance in humans [67], a number of studies have evaluated potential interactions between third-generation AIs and tamoxifen. In contrast, coadministration of exemestane and tamoxifen showed no evidence of pharmacokinetic interaction relative to either agent alone [70, 71]. More recently, no pharmacokinetic interaction was found by giving exemestane in combination with the SERM raloxifene [32]. Clinical trials have shown aromatase inhibitors were well tolerated, even at high doses.[27]There is no established dose of aromatase inhibitors considered life-threatening.

Hormone therapy for breast cancer

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. The heightened gonadotropin levels also upregulate the aromatase promoter, increasing aromatase production in the setting of increased androgen substrate. This would counteract the effect of the aromatase inhibitor in premenopausal women, as total estrogen would increase. The aromatase inhibitors anastrozole and letrozole are approved to be given to postmenopausal women as initial therapy for metastatic or locally advanced hormone-sensitive breast cancer (12, 13). Both of these drugs and the aromatase inhibitor exemestane are also approved to treat postmenopausal women with advanced breast cancer whose disease has worsened after treatment with tamoxifen (14).

Clinical findings from the Arimidex, Tamoxifen, Alone or in Combination trial demonstrated that the combination of anastrozole and tamoxifen was not more efficacious than tamoxifen alone [66]. Previous studies combining aminoglutethimide and tamoxifen in patients with metastatic disease also revealed no superiority compared with either monotherapy [67]. The corresponding randomized study comparing a tamoxifen and steroidal AI combination with tamoxifen alone has not yet been performed. The validity of these explanations, as well as any optimal treatment sequence for resistant disease (e.g., nonsteroidal followed by steroidal versus steroidal followed by nonsteroidal), remains to be determined.