Systemic treatment for triple negative breast cancer (TNBC: negative for the expression of estrogen receptor and progesterone receptor and HER2 amplification) has been limited to chemotherapy options. Neoadjuvant chemotherapy induces tumor shrinkage and improves the surgical outcomes of patients with locally advanced disease and also identifies those at high risk of disease relapse despite today’s standard of care. By using pathologic complete response as a surrogate endpoint, novel treatment strategies can be efficiently assessed. Tissue analysis in the neoadjuvant setting is also an important research tool for the identification of chemotherapy resistance mechanisms and new therapeutic targets. In this paper, we review data on completed and ongoing neoadjuvant clinical trials in patients with TNBC and discuss treatment controversies that face clinicians and researchers when neoadjuvant chemotherapy is employed. 1. Introduction Neoadjuvant chemotherapy, also known as preoperative or primary systemic therapy, is an option for patients with breast cancers who require cytotoxic chemotherapy. It was initially used for patients with locally advanced inoperable breast cancers [1]. Subsequently tumor regression induced by chemotherapy allows a proportion of patients with large operable cancers who hitherto required a mastectomy to achieve breast conservation. For example, the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 clinical trial randomized a large number of women to receive chemotherapy either pre- or postoperatively [2]. Although there were no survival differences, preoperative chemotherapy improved the rate of breast conservation. In those who are already candidates for breast conservation, neoadjuvant chemotherapy may also result in a more desirable cosmetic outcome by allowing less extensive surgery. In addition, neoadjuvant treatment provides a critical opportunity to assess the in vivo responsiveness to chemotherapy and a research platform for investigations of tissue or imaging predictors of response and novel therapeutic targets. Neoadjuvant chemotherapy has therefore increasingly become a preferred strategy for patients with Stage II or III breast cancers. Triple negative breast cancer (TNBC) is defined clinically by the absence of estrogen receptor (ER), progesterone receptor (PgR), and HER2/neu overexpression and encompasses a molecularly diverse group of diseases. As TNBC lacks a clearly defined therapeutic target, patients receive chemotherapy for their systemic management. Since chemotherapy-resistant TNBC carries a
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