Neoadjuvant endocrine therapy for breast cancer: an overlooked option?

For many oncologists, neoadjuvant treatment for breast cancer is synonymous with preoperative cytotoxic chemotherapy, regardless of tumor characteristics. Preoperative therapy with an endocrine agent is generally considered suitable only for the frail elderly or the medically unfit. However, favorable information regarding third-generation aromatase inhibitors in the treatment of all stages of breast cancer prompts a reconsideration of this bias. In light of the fact that neoadjuvant therapy with aromatase inhibitors is restricted to postmenopausal women with strongly estrogen-receptor-positive tumors, the assumption that neoadjuvant combination chemotherapy is more efficacious than a third-generation aromatase inhibitor can be reasonably questioned. It is particularly remarkable that the outcome of a comparison of adjuvant tamoxifen vs anastrozole (Arimidex)--the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial--in more than 6,000 patients was predicted by a neoadjuvant trial that showed an efficacy advantage for a third-generation aromatase inhibitor (letrozole [Femara]) compared to tamoxifen in a sample of 337 patients after only 4 months of treatment. The potential of the neoadjuvant setting in efforts to identify new biologic agents that could build on the effectiveness of adjuvant aromatase inhibitors is therefore beginning to be appreciated. Finally, neoadjuvant therapy with an aromatase inhibitor could be considered a sensitivity test of endocrine therapy that might be incorporated into strategies to individualize treatment according to response. For this possibility to be realized, however, a better understanding of the relationship between surrogates from the neoadjuvant setting and the long-term outcome of adjuvant aromatase inhibitor therapy will have to be established through practice-setting clinical trials.