Aromatase Inhibitors: A New Reality for the Adjuvant Endocrine Treatment of Early-Stage Breast Cancer in Postmenopausal Women

Tamoxifen, a selective estrogen receptor modulator (SERM), has been used for many decades as the “gold standard” adjuvant treatment for patients with hormonereceptor- positive early breast cancer. This drug, when administered for 5 years, reduces the risk for recurrence, contralateral breast cancer (BC) and death. These benefits have been observed up to 15 years and are independent of the patient’s age, menopausal status, nodal status, hormonal receptor status, and the use of adjuvant chemotherapy. The optimal duration of tamoxifen in the adjuvant setting has not been established yet, but it has been demonstrated that 5 years are better than shorter treatment while it is still unclear if a prolongation of the treatment for more than 5 years is worthwhile. Tamoxifen is usually well-tolerated, but important adverse events such as endometrial cancer, cerebrovascular accidents and thromboembolic events can occur, and the increase in absolute risk of these adverse events appears to be age-correlated.

In the last decade, third generation aromatase inhibitors (AIs), either steroidal (exemestane) or non-steroidal (anastrozole, letrozole), have shown to be an effective alternative to tamoxifen in postmenopausal patients with BC regardless of its stage. These agents act by blocking the aromatase enzyme which converts androgens into estrogens. Trials comparing AIs to tamoxifen in postmenopausal women with metastatic disease have shown a superiority of AIs over tamoxifen and a more favourable safety profile. In the adjuvant setting, AIs have been shown to be more effective than tamoxifen given for 5 years either in the up-front administration or after 2-3 years (early switch). Two randomised trials which have evaluated the two strategies of AIs administration have shown superimposable results in terms of efficacy with AIs given up-front or in sequence to tamoxifen. AIs seem to give benefits in comparison to placebo if given after 5 years (late switch) of tamoxifen. At the moment, therefore, the treatment decision should be based on individual factors such as risk of relapse, absolute benefit, and comorbidities.

Keywords: Adjuvant endocrine therapy, aromatase inhibitors, breast cancer, postmenopausal women.