Neoadjuvant hormonal treatment of locally advanced breast cancer

The potential goals of neoadjuvant treatment for locally advanced breast cancer (LABC) include downsizing tumors to allow breast conservation as well as the possibility of improving survival rates. Most of the published evidence relates to the use of neoadjuvant chemotherapy rather than hormonal therapy. However, it has been well established that adjuvant hormonal therapy is the most effective adjuvant treatment of hormone-sensitive tumors, particularly in post-menopausal women. It is therefore logical to hypothesize that neoadjuvant hormonal therapy is as least as effective as chemotherapy in these patients. Earlier studies of neoadjuvant hormonal therapy in LABC focused primarily on elderly patients, especially those who were unsuitable for either surgery or chemotherapy. Most often, patients were unselected for the hormonal receptor status of their tumor. During the 1980s and early 1990s, several nonrandomized phase II studies were published testing the effectiveness of tamoxifen as primary therapy for elderly women (age ≥70 years) with locoregional breast cancer. Response rates 49–68% were observed. The survival rate was comparable to historical data with conventional methods of treatment. The Introduction: of third-generation aromatase inhibitors (AIs) has encouraged studies to compare the efficacy of AIs with tamoxifen not only in adjuvant and metastatic but also in the neoadjuvant setting. The trials LET 024, IMPACT and PROACT and some other smaller studies were compared different AIs with tamoxifen in postmenopausal breast cancer patients with hormone receptor positive tumors. These trials have shown similar or better efficacy of AIs comparing with tamoxifen. There are limited observations on different efficacy of AIs and tamoxifen in HER1/2+ disease and on predictive value of Ki67 changes for response to AIs. Neoadjuvant hormonal therapy with AIs is now being explored in a younger, healthier population of postmenopasusal breast cancer patients. Such trials will allow us not only to study standard efficacy end points but also to find predictive biomarkers of disease and may provide insight into therapy resistance and sensitivity.