Choosing between an aromatase inhibitor and tamoxifen in the adjuvant setting

Approximately three-quarters of all invasive breast tumors are estrogen and/or progesterone receptor-positive. The selective estrogen receptor modulator tamoxifen has been the preferred endocrine therapy for almost four decades. One of the most significant advances in endocrine therapy for women after menopause with early breast cancer is the introduction of third-generation aromatase inhibitors as an alternative or as an additional treatment to tamoxifen therapy. In making a choice between the use of an aromatase inhibitor or tamoxifen in the adjuvant setting, a careful analysis of both the efficacy data and toxicity profiles of each drug is essential.

In the adjuvant setting, three major randomized controlled trials have reported on the use of three different aromatase inhibitors for women after menopause with breast cancer. In all of these trials, the third-generation aromatase inhibitors demonstrated significantly improved disease-free survival, either compared with tamoxifen as an initial adjuvant hormonal therapy, or when aromatase inhibitors were given sequentially after tamoxifen therapy. The toxicity data suggest that bone loss, increased fracture rates, and other musculoskeletal disorders are the most serious side effects associated with the use of aromatase inhibitors. Toxicities commonly associated with tamoxifen therapy such as thromboembolic events and endometrial abnormalities are reduced in patients receiving aromatase inhibitors, however.

The present data demonstrate the improved efficacy achieved with third-generation aromatase inhibitors compared with tamoxifen and support the use of these agents in the adjuvant setting. The optimal treatment strategy for whether these agents should be given in place of tamoxifen or as part of a sequential treatment has yet to be defined, however. Moreover, to be able to optimize treatment with aromatase inhibitors, it is imperative to develop interventions to prevent or alleviate treatment related side effects.