Neoadjuvant endocrine therapy for breast cancer: past, present and future

Combined treatments together with surgery, radiotherapy, chemotherapy, and endocrine therapy have contributed substantially to the improved survival rate in breast cancer. For more than 2 decades, tamoxifen has been the standard endocrine agent for hormone receptor-positive tumors. Third-generation aromatase inhibitors have, however, now proven to be superior to tamoxifen in the adjuvant and, more recently, the neoadjuvant treatment of postmenopausal patients. They have especially improved the surgical management of large or inoperable locally advanced breast tumors. Other advantages of neoadjuvant endocrine therapy are just emerging, but there are still many unanswered questions regarding its optimal use in this setting. A need to define how to select the patients who will benefit most from these therapies, the optimal duration of treatment, the best method to evaluate the treatment response achieved, the existence of predictive factors for response, or the superiority of certain endocrine agents over others has been observed. Other questions regarding which complementary local and systemic treatments should be administered after neoadjuvant endocrine therapy or which efficacy endpoints should be evaluated in clinical trials are also of interest. To answer as many of these questions as possible, we have carried out a critical analysis of the current literature on the use of endocrine therapy in the neoadjuvant setting of breast cancer. In this review, we outline the rationale for its use, and consider data published to date to further clarify how to optimize its administration.