Adjuvant therapy with aromatase inhibitors in postmenopausal, estrogen receptor- positive breast cancer patients: upfront or sequential?

For decades tamoxifen (TAM) has been the mainstay hormonal treatment for estrogen receptor positive (ER+) breast cancer patients. Nevertheless, during the last years, for postmenopausal women particularly, the third generation aromatase inhibitors (AI) became the preferred alternative. The results of the randomized trials showed that AI were superior to TAM in terms of efficacy, and were accompanied by a different but fairly convenient side effects profile. Subsequently, all updated guidelines recommend the use of AI in the adjuvant setting for this category of patients, either upfront, following 2-3 years of TAM or as extended adjuvant therapy, after 5 years of TAM. However, no consensus has been reached regarding the best strategy to be used, and the expert opinion is divided, based on the available evidence. The controversial aspect of whether AI should be used upfront or following 2-3 years of TAM is further detailed in this manuscript, and some useful recommendations are provided in order to facilitate the decision-making process during the current clinical practice.