Triple negative breast cancer is an aggressive form of breast cancer with limited treatment options and is without proven targeted therapy. Understanding the molecular basis of triple negative breast cancer is crucial for effective new drug development. Recent genomewide gene expression and DNA sequencing studies indicate that this cancer type is composed of a molecularly heterogeneous group of diseases that carry multiple somatic mutations and genomic structural changes. These findings have implications for therapeutic target identification and the design of future clinical trials for this aggressive group of breast cancer. 1. Introduction Triple negative breast cancer (TNBC) is defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and HER-2 Overexpression. It accounts for 15–20% of all breast cancer cases [1, 2], but occurs at a higher frequency in young premenopausal women with African Ancestry (AA) [3]. High body mass index (BMI) and high parity, instead of low parity in other types of breast cancer, have been associated with increased risk for TNBC [4–6]. TNBC is associated with an overall poor prognosis as exemplified by a higher rate of early recurrence and distant metastasis to brain and lungs compared to other breast cancer subtypes [7, 8]. The unfavorable clinical outcome is partly explained by its aggressive pathologic features including a higher histology grade and mitotic index [9]. Chemotherapy is the only systemic therapy currently available for TNBC and is curative in a subset of patients with chemotherapy-sensitive disease. A higher rate of pathologic complete response (pCR) to standard chemotherapy has been observed in patients with TNBC compared to ER+ disease. A pCR rate of 22% in TNBC versus 11% in ER+ disease was reported in a study of over 1？000 patients treated with neoadjuvant anthracycline and taxane-based chemotherapy regimens [10]. The excellent outcome associated with the pCR, however, is in contrast to the high risk of recurrence and cancer-related deaths in those with residue disease. Although alternative agents such as platinum compounds have demonstrated promising activity, up to 70–80% of patients have residual cancer following neoadjuvant cisplatin [11]. In the metastatic setting, TNBC is typically associated with an initially higher response rate, but in a shorter time to progression following treatment with existing chemotherapy agents, resulting a shorter overall survival compared to ER+ breast cancer in multiple studies [12]. The underlying molecular mechanism for this paradox is yet to be
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