Cancer Treatment Reviews 36S3 (2010) S80–S86 Contents lists available at ScienceDirect Cancer Treatment Reviews journal homepage: www.elsevierhealth.com/journals/ctrv Treatment of triple negative breast cancer (TNBC): current options and future perspectives M. De Laurentiis a,b, *, D. Cianniello b , R. Caputo b , B Stanzione b , G. Arpino b , S. Cinieri c,d , V. Lorusso e , S. De Placido b a Department of Breast Oncology, National Cancer Intitute “Fondazione Pascale”, Naples, Italy b Department of Endocrinology and Molecular and Clinical Oncology, University “Federico II”, Naples, Italy c Oncology Department & Breast Unit, “A. Perrino” Hospital, Brindisi, Italy d Medical Department, European Institute of Oncology, Milano, Italy e Division of Medical Oncology, “Vito Antonio Fazzi” Hospital, Lecce, Italy article info Keywords: Breast cancer Triple negative Basal-like PARP inhibitors EGFR inhibitors Antiangiogenics summary Breast cancer is not considered anymore a unique disease. Microarray gene expression analysis led to the identification of 4 major breast cancer “intrinsic” subtypes, including hormone receptor (HR)-positive luminal A and B, human epidermal growth receptor 2 (HER2)-positive and basal- like breast cancer (BLBC). These subtypes have distinct phenotypes, molecular profiles, clinical behaviour and response to therapy, with the BLBC carrying the worst outcome. Microarray analysis is not feasible in routine practice and therefore oncologists rely on a simpler immunohistochemical (IHC) classification to identify relevant breast cancer subtypes. Triple negative breast cancer (TNBC) is defined by the absence of oestrogen receptor, progesterone receptor and HER2 expression at IHC analysis. TNBC is strictly related to BLBC and, given the lack of common therapeutic targets, represent a major challenge for breast oncologist. In this review we will summarize the updated knowledge on TNBC, with emphasis on its current treatment and on the new therapeutic options under development. © 2010 Elsevier Ltd. All rights reserved. Introduction Breast cancer (BC) is the most common female cancer. It affects more than 1 million women worldwide and about 400 000 patients die due to this disease every year. 1 BC is a heterogeneous disease consisting of distinct entities characterized by different gene expression patterns. Gene expres- sion array analysis led to the identification of 4 major breast cancer subtypes (so-called “intrinsic subtypes”), including hormone receptor (HR)-positive luminal A and B, human epidermal growth receptor 2 (HER2)-positive and basal-like beast cancer (BLBC). 2 Such subtypes have diverse histopathologic, molecular and clinical features and require different therapeutic approaches. Gene expression array analysis is cumbersome and costly and thus is not routinely performed to identify BC subtypes. A clinically relevant subtype classification is, however, usually obtained by immunohistochemical (IHC) analysis of the tumour expression of oestrogen receptors (ER), progesterone receptors (PgR) or HER2. Using this simple analysis it is possible to identify 3 major BC subtypes: the ER/PgR-positive, or hormone receptor-positive *Corresponding author. Michele De Laurentiis. Department of Breast Oncology, National Cancer Institute “Fondazione Pascale”, via Mariano Semmola, Naples, Italy. Tel.: +390815903599. E-mail address: delauren@unina.it (M. De Laurentiis). (HR-positive) subtype, which basically includes the Luminal A and B intrinsic subtypes and which is potentially sensitive to hormonal treatment; the HER2-positive subtype (approximately corresponding to the homonym intrinsic subtype) which is potentially sensitive to trastuzumab, lapatinib and other HER2- directed targeted drugs; the TNBC subtype, which lacks of the expression of all the three receptor (ER, PgR and HER2) and is, therefore, insensitive to the standard targeted drugs against BC (i.e., hormones and anti-HER2). TNBC accounts for approximately 15% of all breast cancer diagnosis, but is responsible for a disproportionate share of mortality. In fact, TNBC is characterized on average by an aggressive clinical course with a poor prognosis. 1,3 Histology of TNBC often includes high grade, high proliferation rate and necrosis. Due to this high proliferation activity, TNBC very often manifests itself as an interval cancer, diagnosed between screening mammograms. Higher incidence of TNBC has been observed in African-American populations and in younger premenopausal patients 4,5 and in pts with increased body weight and metabolic syndrome. 1 Compared with HR-positive or HER2-positive patients, patients with TNBC have higher likelihood of distant recurrence (HR 2.6, 95% CI 2.0–3.5; p < 0.0001) and death (HR3.2; 95% CI2.3–4.5; p < 0.001). 4,6 The peak risk of recurrence occurs within the first three years after initial treatment of the disease with the majority of deaths occurring 0305-7372/$ – see front matter © 2010 Elsevier Ltd. All rights reserved.