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Breast Cancer Triple Negative Breast Cancer Pathologic Diagnosis and Current Chemotherapy Treatment Options Bernardo L Rapoport, MD, MMed Int Med (Wits), 1 Simon Nayler, BSc, MBBCh, FCPath, MMed, 2 Georgia S Demetriou, MBBCh (Wits), FCP (SA), Cert Med Onc (SA), 3 Shun D Moodley, MBBCh (Wits), FCP (SA) 4 and Carol A Benn, MBBCh (Wits) FCS (SA) 5 1. Specialist Physician and Medical Oncologist, The Medical Oncology Center of Rosebank, Johannesburg, South Africa; 2. Specialist Histopathologist, Gritzman and Thatcher Inc. and Wits Donald Gordon Medical Center, Johannesburg, South Africa; 3. Specialist Physician and Medical Oncologist, Department of Internal Medicine Division of Medical Oncology, University of the Witwatersrand and Wits Donald Gordon Medical Center, Johannesburg, South Africa; 4. Specialist Physician and Medical Oncologist, University of the Witwatersrand and Wits Donald Gordon Medical Center, Johannesburg, South Africa; 5. Specialist Surgeon, Netcare Milpark Hospital Breast Centre and Helen Joseph Hospital, University of the Witwatersrand, Johannesburg, South Africa Abstract Triple negative breast cancer (TNBC) comprises 12–20 % of all breast cancers and are a heterogeneous group of tumors, both clinically and pathologically. These cancers are characterized by the lack of expression of the hormone receptors estrogen receptor (ER) and progesterone receptor (PR), combined with the lack of either overexpression or amplification of the human epidermal growth factor receptor-2 (HER2) gene. Conventional cytotoxic chemotherapy and DNA damaging agents continue to be the mainstay of treatment of this disease in the neoadjuvant, adjuvant, and metastatic setting. The lack of predictive markers in identifying potential targets for the treatment of TNBC has left a gap in directed therapy in these patients. Platinum agents have seen renewed interest in TNBC based on an increasing body of preclinical and clinical data suggesting encouraging activity. However, comparisons between chemotherapy regimens are mostly retrospective in nature and the best agents or drug combinations for TNBC have not been established in prospective randomized trials. Numerous studies have now shown that TNBC has significantly higher pathologic complete response (pCR) rates compared with hormone receptor positive breast cancer when treated with neoadjuvant chemotherapy, and pCR correlates well with better outcomes for these patients. Patients with TNBC account for a larger number of deaths in the setting of metastatic breast cancer. There is no preferred treatment for the first-line metastatic setting. Although individual agents are recommended, given the often aggressive nature of TNBC and the presence of extensive visceral disease, the use of a combination of drugs, rather than a single agent, is often advocated. This review article will outline the pathologic diagnosis of TNBC and the treatment options available to these patients in the neoadjuvant, adjuvant, and metastatic setting, including an assessment of future directions of treatment. Keywords Breast cancer, triple negative, pathological diagnosis, chemotherapy treatment, neoadjuvant, targeted treatment, adjuvant, metastatic Disclosure: The authors have no conflicts of interests to declare. Received: January 20, 2014 Accepted: March 30, 2014 Citation: Oncology & Hematology Review, 2014;10(1):25–32 Correspondence: Bernardo L Rapoport, MD, MMed Int Med (Wits), The Medical Oncology Centre of Rosebank, 129 Oxford Road, Saxonwold 2196, Johannesburg, PO Box 2040, Parklands 2121, South Africa. E: brapoport@icon.co.za The treatment of triple negative breast cancer (TNBC) is an unmet medical need, which refers to tumors that are estrogen receptor (ER) and progesterone receptor (PR) negative, and where human epidermal growth factor receptor 2 (HER2) is not overexpressed. This subset accounts for approximately 12–20  % of breast cancer patients. 1 Gene expression analysis on this heterogenous group of patients demonstrates an overlap between the molecular signature of TNBC and basal-like (BL) breast cancer (BLBC). The concordance rates between the two groups are in the order of 70–90 %. Not all TNBC can be defined as BLBC as a small minority of BLBC patients express ER and HER2 receptors. The purpose of this review is to discuss the pathologic diagnosis, current trends in management of TNBC © To u ch MEd ica l MEdia 201 4 in the neo-adjuvant, adjuvant, and metastatic disease treatment, and future directions. Pathologic Features and Diagnosis of Triple Negative Breast Cancer TNBC, which comprises 12–20 % of all breast cancers, are a heterogeneous group of tumors, clinically and pathologically at the molecular level. 1 The defining features of this cohort of breast cancers are a lack of expression of the hormone receptors ER and PR, combined with a lack of either overexpression or amplification of the HER2 gene. The majority (around 70 %) has been demonstrated to be BLBC, and this subtype is defined by an 25