[NEOADJUVANT TREATMENT OF LOCALLY ADVANCED ESTROGEN/PROGESTERONE POSITIVE, HER2NEU NEGATIVE BREAST CANCER]

Women who present with locally advanced breast cancer that would require a mastectomy are often recommended to undergo chemotherapy prior to surgery in hopes of down-staging the tumor and allowing for breast-conserving surgery. This approach is very effective in women with triple negative and Her2neu positive locally advanced breast cancer, yet the results in ER/PR positive (luminal) breast cancers have been less effective. In post-menopausal women, neoadjuvant hormonal treatment in such cases can cause tumor regression and allow for breast-conserving therapy, in some patients. In premenopausal women with locally advanced luminal type breast cancer, neoadjuvant hormonal therapy can also be effective and is a valid option according to the NCCN guidelines. Yet, there remains a sense that perhaps treatment of this group of patients with chemotherapy results in better outcomes. For the past fifteen years various molecular profiles of luminal breast cancers have been studied and have been used to help guide decisions as to the benefit of adjuvant treatment - whether chemotherapy is necessary or hormonal therapy alone would be adequate. In the neo-adjuvant setting, these profiles can also help predict which tumors are likely to respond to chemotherapy and which are less likely to respond. The only hormonal drugs available until very recently for use in the neoadjuvant setting were either Tamoxifen or an aromatase inhibitor. In the past few years a new class of drugs, CDK4/6 inhibitors have been developed and approved and have significantly improved response rates and time to progression in patients with metastatic hormone responsive breast cancer, and they have also been studied in small trials in the neoadjuvant setting. In this article we will review the data that is available to help guide the optimal choice of treatment in women who present with locally advanced luminal breast cancers including the use of molecular profiles and the potential role of anti-CDK 4/6 drugs.