Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Abstract

Breast cancer is the most prevalent type of cancer in women and responsible for significant female cancer-related mortality worldwide. In the Western world, over 80% of breast cancers are hormone-receptor positive for which endocrine therapy is administered. The main anti-estrogen treatments in use consist of selective estrogen-receptor modulators, such as tamoxifen, and third-generation aromatase inhibitors (AIs), such as exemestane, letrozole, and anastrozole. In this review, the focus will lie on exemestane, its clinical use, and its side-effect profile. Exemestane is the only third-generation steroidal AI. Its efficacy as a first-line treatment in metastatic breast cancer has been demonstrated. Therefore, exemestane could be considered a valid first-line therapeutic option, but it also can be used in second-line or further situations. Exemestane is mostly used as part of sequential adjuvant treatment following tamoxifen, but in this setting it is also active in monotherapy. Furthermore, this AI has been studied in the neoadjuvant setting as presurgical treatment, and even as chemoprevention in high-risk healthy postmenopausal women. It may reverse side effects of tamoxifen, such as endometrial changes and thromboembolic disease but may also cause some inconvenient side effects itself. Additionally, there is a lack of total crossresistance between exemestane and nonsteroidal AIs as far as their anti-tumoral efficacy is concerned; moreover the two classes of AIs display a nontotal overlapping toxicity profile. Taking together, exemestane can be considered as a useful treatment option at all stages of breast cancer.

AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules

“…Patients with HR þ advanced breast cancer typically respond well to endocrine therapies and antiestrogen modalities, such as aromatase inhibitors (anastrazole, letrozole, and exemestane; ref. 14), tamoxifen (15) or fulvestrant (16). Although aromatase inhibitors have become standard of care in postmenopausal women and endocrine therapy is generally very effective, disease progression remains a major challenge in this setting.…”

Aromatase inhibitors for prevention of breast cancer in postmenopausal women

“…73 AI-associated arthralgia syndrome is an increasingly recognized estrogen deprivation phenomenon that occurs in 30% to 40% of women and is disabling in 5% to 10% of women. 74<76 However, in clinical practice, up to 50% of women complain of musculoskeletal adverse effects.…”

“…74<76 However, in clinical practice, up to 50% of women complain of musculoskeletal adverse effects. 73 These potent hypoestrogenic effects may lead to nonadherence. 77 Interestingly, in the IBIS-II trial, documented arthralgia (of any severity) was high in both the experimental arm and the placebo arm at 51% and 46%, respectively (risk ratio, 1.10; 95% CI, 1.03-1.18).…”

Mechanism of Bushen Jianpi decoction in preventing and treating osteoporosis caused by aromatase inhibitors in breast cancer treatment

“…Since aromatase inhibitors (AIs) are the first choice of drug for postmenopausal patients under endocrine therapy, patients using AIs often suffer from fractures, muscle and joint pain, and other symptoms that seriously affect quality of life. There is an urgent need to address and prevent this problem [2,3]. The key to bone-related events is that bone metabolic imbalances are caused by the decrease in estrogen levels [4].…”