What is triple-negative breast cancer? William J. Irvin Jr., Lisa A. Carey * Department of Medicine, Division of Hematology/Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, CB 7305, 170 Manning Drive, Chapel Hill, NC 27599-7305, USA ARTICLE INFO Article history: Received 28 April 2008 Accepted 25 September 2008 Available online 12 November 2008 Keywords: Breast cancer Basal-like Triple negative Prognosis Molecular profiling Chemotherapy ABSTRACT Triple-negative (ER-negative, PR-negative, HER2/neu not overexpressed) breast cancer has distinct clinical and pathologic features, and is a clinical problem because of its relatively poor prognosis, aggressive behaviour and lack of targeted therapies, leaving chemotherapy as the mainstay of treatment. Most triple-negative tumours fall into the basal-like molec- ular subtype of breast cancer, but the terms are not completely synonymous. Among the intriguing characteristics of triple-negative breast cancer is its association with cancers arising in BRCA1 mutation carriers, in young women and in African–American women. The reasons for these associations are unclear but may ultimately provide avenues for pre- vention and targeted therapy. This review discusses the definitions and characteristics of as well as current and evolving therapies for triple-negative and basal-like breast cancer. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction In 2007, 1.3 million women worldwide were diagnosed and 465,000 died from breast cancer making this the most common cancer in women and the leading cause of death. 1 Though impressive, these statistics treat breast cancer as a homoge- neous entity, which we increasingly recognise as inaccurate. Gene expression studies have identified several major sub- types of breast cancer 2 : the luminal subtypes, which typically express hormone receptor-related genes, and two hormone receptor-negative subtypes – the human epidermal growth fac- tor receptor 2 (HER2) positive/oestrogen receptor (ER) negative subtype and the basal-like subtype. The subtypes vary in prog- nosis, with worse outcomes traditionally seen among the two hormone receptor-negative subgroups compared with the luminal subgroups 3–5 ; however, improvements in chemother- apy, endocrine therapy and HER2-targeted therapy may change the prognostic landscape of breast cancer. A subtype of particular interest is the basal-like breast cancer BBC. In population-based studies, this subtype com- prises approximately 15–20% of breast cancers. 6–8 In research studies, BBC has been reproducibly identified using gene expression methods 4,5 and immunohistochemistry, 9–11 how- ever, a validated method to identify BBC and other intrinsic subtypes of breast cancer for clinical use does not exist. In ar- rays, BBCs are characterised by low expression of ER-related genes and HER2-related genes; for this reason in clinical spec- imens they are usually ER-negative, progesterone receptor (PR) PR-negative and lack HER2 overexpression. This is called the ‘triple-negative’ phenotype. Since triple-negative breast cancer is resistant to our cur- rent HER2-targeted therapies such as trastuzumab, and hor- monal therapies such as tamoxifen and aromatase inhibitors, chemotherapy is the mainstay of treatment. This lack of targeted therapies has intensified the interest in this group of patients. This review will focus on the definition and features of triple-negative breast cancer, current treat- ment strategies and future directions for treatment. 2. Nomenclature As mentioned above, most triple-negative breast cancers cluster with the BBC, 10 however, these are not synonyms. ‘Tri- ple negative’ is a term based upon clinical assays for ER, PR 0959-8049/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2008.09.034 * Corresponding author: Tel.: +1 919 966 8218; fax: +1 919 966 6735. E-mail address: Lisa_Carey@med.unc.edu (L.A. Carey). EUROPEAN JOURNAL OF CANCER 44 (2008) 2799 – 2805 available at www.sciencedirect.com journal homepage: www.ejconline.com