Neoadjuvant Therapy for HER2-positive Breast Cancer

In HER2-positive early breast cancer, neoadjuvant treatment with a combination of sequential chemotherapy and HER2-targeted therapy is currently the standard of care. This is followed by breast surgery, radiotherapy (if indicated), completion of 12 months of HER2-directed therapy, and - depending on the tumor biology - endocrine adjuvant therapy, and ultimately follow up. 10-year survival rates in the HER2-positive subgroup of breast cancer do reach now more than 75% with the introduction of first adjvuant and later neoadjuvant HER2-targeted therapies over the last 15 years. The neoadjvuant setting helps to downstage locally advanced tumors, to provide early information of tumor response, to assess the efficacy of new therapies in vivo, to reduce treatment duration, and to introduce new targeted therapies into the clinical routine. It also allows enrolling fewer patients into clinical trials in order to reach adequate effects in clinical outcome. The neoadjuvant approach and our interest in this setting are based on pCR (pathological complete response) and its translation into better long-term outcome. In recent trials, we have reached more than 60% pCR with a subsequent improvement of DFS and hopefully OS. Therefore, chemotherapy schedules and new HER2-targeted agents such as lapatinib, pertuzumab, and T-DM1 have been introduced into the neoadjuvant setting. To balance over- and undertreatment, current trials include personalized concepts and assess new biomarkers and tumorbiological factors. We have learned for example to differentiate between HR (hormone receptor)-positive and -negative tumors in the HER2-positive population. Depending on pCR or non-pCR after neoadjuvant treatment, the adjuvant therapy may be adjusted. This concept of post-neo-adjuvant trials is now entering the field of strategies in the neoadjuvant setting for HER2-positive non-metastatic primary breast cancer. The 2017 standard of care in the neoadjuvant setting according to national and international guidelines combines a taxane-containing chemotherapy with a dual blockade of trastuzumab and pertuzumab. This review will point out current trials and their strategies to continue improving outcome and reduce morbidity as well as mortality in HER2-positive early breast cancer.