Triple-negative breast cancer (TNBC) is an aggressive malignancy with a poor prognosis despite the high rates of response to chemotherapy. This scenario highlights the need to develop novel therapies and/or treatment strategies to reduce the mortality associated with TNBC. The neoadjuvant setting provides a model for rapid assessment of treatment efficacy with smaller patient accruals and over shorter periods of time compared to the traditional adjuvant setting. In addition, a clear surrogate endpoint of improved survival, known as pathologic complete response, already exists in this setting. Here, we review current data from completed and ongoing neoadjuvant clinical trials for TNBC. 1. Introduction Triple-negative breast cancer (TNBC) is defined histologically as invasive carcinoma of the breast that lacks staining for estrogen receptor, progesterone receptor, and HER2/neu. Approximately 15–20% of breast cancers illustrate this phenotype [1]. TNBC is associated with high proliferative rates, early recurrence, and poor survival rates. This aggressive disease is insensitive to widely used targeted therapies such as trastuzumab and endocrine therapies, tamoxifen and aromatase inhibitors, which have been effective at reducing breast cancer mortality. Younger women and women of African descent have a high prevalence of TNBC [1]. There are limited and often ineffective therapeutic treatment options for patients with stage IV TNBC. 2. The Concept of Neoadjuvant Chemotherapy The use of neoadjuvant chemotherapy for patients with locally advanced breast cancer has increased significantly over several decades. Neoadjuvant chemotherapy was first used in patients with unresectable or marginally resectable breast cancer [2, 3]. The results from initial studies showed high rates of tumor response and regression. Additional clinical trials were performed with the primary objective of determining whether breast conserving surgery could be offered after neoadjuvant chemotherapy to patients who would have traditionally required mastectomy. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 study randomized 1,523 women with operable breast cancer to receive 4 cycles of adriamycin and cyclophosphamide either in the preoperative or postoperative setting [4]. This study showed that neoadjuvant chemotherapy improved breast conservation rates (67.8% versus 59.8%). Although there was no difference in overall survival (OS) between neoadjuvant and adjuvant therapy groups, patients treated in the neoadjuvant setting whose tumors obtained a pathologic complete
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