# New Achievements for the Treatment of Triple-Negative Breast Cancer
## 1 Introduction  
Breast cancer (BC) is one of the most frequent types of cancer among women. The global cancer project (GLOBOCAN, 2012) reports that breast cancer is considered the second most common disease in the world [1]. It is the second leading cause of death among women worldwide and receives increasing attention nowadays [2]. In high income countries, BC mortality is decreasing, largely owing to improved laboratory, epidemiological and clinical research, but incidence has been steadily increasing [3, 4]. Therefore, it is urgent to develop new treatment regimens and targets [5], and for this reason numerous research studies are directed towards new strategies for the treatment of BC [6, 7, 8, 9]. Among BCs, triple-negative breast cancer (TNBC), which does not express estrogen receptor (ER) or progesterone receptor (PR) and does not overexpress the human epidermal growth factor receptor 2 (HER2), is one of the most aggressive subtypes. TNBC includes the more common invasive ductal and lobular carcinomas plus rarer subtypes of BC [10]. The latest classification divides TNBC into four different subtypes: basal-like 1 (BL1), basal-like 2 (BL2), mesenchymal stem cell-like (MSL) and luminal androgen receptor (LAR) [11]. TNBC is a heterogeneous disease, with subtypes characterized by distinct pathologic, genetic, and clinical features [12]. Its clinical features include high invasiveness, high metastatic potential, proneness to relapse and poor prognosis. It accounts for approximately 15% to 20% of all BCs [13]. Cancer stem cells (CSCs), also called tumor initiating cells (TICs), seem to contribute to aggressive phenotypes of TNBC [14]. Brain metastasis (BM) is a serious, life-threatening issue that occurs more frequently in TNBC patients, and TNBC has a worse prognosis than other BCs [15; 16]. The identification of TNBC with a high level of accuracy compared with other tumor sub-types is due to magnetic resonance imaging (MRI) [17]. As TNBC ER and PR expression and do not overexpress HER2, they are not sensitive to endocrine therapy or HER2 treatment, and standardized TNBC treatment regimens are still lacking. A large number of novel therapeutic agents have been evaluated for their efficacy in TNBC [18]. TNBC has traditionally been treated with systemic chemotherapy (e.g., paclitaxel, capecitabine, eribulin, ixabepilone) [19]. However, standard chemotherapy is associated with low response rates and short progression-free survival, especially among patients with pretreated metastatic triple-negative breast cancer (mTNBC). Indeed, the predominant systemic therapy for most mTNBC remains chemotherapy, but responses are often short-lived, and patients have a median overall survival (OS) of 12 to 18 months [20]. Moreover, various sensitivities of cancer sufferers critically limit chemotherapy's clinical results due to infection, antibiotic resistance [21], diverse pathogens, individual differences and chemotherapy resistance [22]. Recent data suggest that matrix alterations in triple-negative cancer cells are epigenetically regulated, and that matrix-associated events increase tumor cell survival and resistance to therapy [23]. Recently, ferptopsis-inducing agents have also been suggested as interesting antitumor candidates [24; 25]. Despite recent treatments, most mTNBC patients have disease progression, and the 5-year OS is estimated at only 11%. TNBC greatly benefits from precision oncology and therapeutic targeting [26; 27]. Targeted agents for TNBC include inhibitors of poly(ADP-ribose) polymerase (PARP), epidermal growth factor receptor (EGFR), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), angiogenesis, microtubules, proto-oncogene tyrosine-protein kinase Src (Src kinase), AKT, checkpoint kinase 1 (Chk1) and mammalian target of rapamycin (mTOR) [28].