Triple- negative breast cancer (TNBC) is a subtype of breast cancer that does not express the estrogen and progesterone receptors and HER2 protein. This type of cancer represents an important clinical challenge because it does not respond to endocrine therapy or anti- HER2 drugs. In this case, the mainstay treatment is the chemotherapy. The diagnosis and management of triple-negative breast cancer is basically using the same standard principles as to those of breast cancer in general and are very similar in the approach. The main approach in having a correct TNBC management, resumes to finding new specific targets that can theoretically improve the outcome of the disease. Breast cancer is one of the most frequent cancer in women and one of the leading cause of death among this category of patients. Triple negative breast cancers represent approximative 10- 20% of all breast cancers diagnosed worldwide. (1)It is well known the importance of the hormone receptors to the biology of the breast cancer and that the human breast cancers are dependent of estrogen and progesterone for growth. This effect is mediated via hormone receptors (estrogen- ER and progesterone- PR receptors). These receptors are usually overexpressed in breast cancers. Thus, new therapies that could interact with the hormone biology were analyzed for finding better treatment and it came clear that endocrine therapy would become an important tool for managing breast cancer. Nowadays, all guidelines recommend that testing for ER and PR should be performed in all invasive breast cancers and the result should select patients that can benefit from endocrine therapy. Immunohistochemistry (IHC) is the essential method used to characterize the ratio of positive cells and the intensity of staining within the cells in all tissues. It is the method of choice for determining the hormone receptors status in breast cancers. There are many scoring systems that can be used to predict the response to therapy and the first system was based on counting the percentage of the positive cells. Therefore, the International Breast Cancer Study Group table, that is representative for the St Gallen basic treatment guidelines; splits the breast cancer into 3 distinctive categories: nonresponsive (0 %), responsive uncertain (1-9%) and responsive (10%). The threshold of 1% positive cells represents the option for endocrine therapy (2). Human epidermal growth factor receptor 2 (HER 2) gene, initially called HER2/neu or ERBB2 encodes a transmembrane receptor HER2, which belongs to the epidermal growth factor receptors family (EGFR). These receptors are important in growth, differentiation and possible angiogenesis (3). The HER2 status is very important in case of a breast tumor because if the conclusion is reached that HER2 played a role in the cancer evolution, the respective patients can be a part in the therapies that target HER2. The HER2 status can be identified by IHC and fluorescence in situ hybridization (FISH). IHC evaluates overexpression of the receptor protein at the surface of the cells, while FISH evaluates the status of the HER2 gene in the nucleus (2). IHC reactions for HER-2 are: 0 and 1+ scores are negative, 2+ is weakly positive and 3+ is positive. If a result is positive for HER- 2, there is not necessary any other further evaluation for invasive cancers. Weakly positive or equivocal or 2+ cases should be tested for gene ampli'''cation by FISH (2). In this review triple-negative will be referred to cancers that have '''1% expression of ER and PR as determined by IHC, and that are either 0-1+ by IHC for HER2, or 2+ and FISH negative, according to ASCO/CAP guidelines 2013 (4).The most obvious and logical hypothesis would be that TNBC and the basal- like tumors are identical. A percentage of 8-37% of all breast cancers are represented by the basal-like (5). They are associated with high histological and nuclear grade with high mitotic and proliferative indices. These tumors have an aggressive clinical expression and tend to metastasize to the brain and lungs. Basal-like tumors do not express ER, PR and HER2 and thus they are referred as triple negative. They also express myoepithelial markers (CK5, CK14, CK17 and laminin) and P- cadherin and EGFR (5, 6). These cancers are associated with mutations of tumor protein 53 gene and microarray and IHC analyses demonstrated that basal-like cancers constitute approximately '' of a BRCA1 gene- related breast cancers (5).It is important to note that the terms triple negative and basal-like are not the completely the same. The triple negative refers to the IHC classification of the breast cancers in which the ER, PR and HER2 are not expressed. The basal-like subtype is expressed via gene expression microarray analysis (7). There is approximative 80% overlap between triple-negative and intrinsic basal-like subtype. Some special histological types (such as medullary and adenoid cystic carcinoma) with low risks of distant recurrence are also included in TNBC (8). TNBC express other markers than the basal ones and can be classified as normal breast-like, molecular apocrine or claudin- low subtype by gene expression profiling (9). Moreover, other histological types of breast cancers exist that have as characteristics not to show the basal-like pattern and they express a triple negative phenotype (pleomorphic lobular carcinomas, apocrine carcinomas a.s.o.) (9). A few triple-negative tumors express luminal markers, such as androgen receptors, with a lower proliferative activity (10). Other markers of TNBC that can potentially be targeted are HER1/ EGFR, c- Kit expression, p53 mutations, poly ADP-ribose polymerase 1 (6).These biological subgroups mix and currently they cannot be combined into a unique model of triple-negative breast cancer biology.General characteristics of TNBCTNBC is characterized by several clinicopathologic features. The majority of TN tumors have a ductal origin, but other phenotypes like metaplastic, adenoid cystic, atypical or typical medullary, can be present (6).The aggressive pattern of TNBC can be suggested by the onset at a younger age, the greater the tumor volume and grade and the greater chance of BRCA1 expression. They are more prevalent in African- American women and there is a high association with obesity or metabolic syndrome (11,12). Other risk factors implied in the disease are younger age at menarche, high parity, full-term pregnancy at a younger age or shorter duration of breastfeeding (6). TNBC are considered interval cancers (they are discovered/detected within the 12 months after a mammographic screening in which findings are considered normal). This is highly suggestive for the rapid progression of the disease and the similarity of the tumor tissue to the normal one (11). Other facts that suggest the aggressive pattern of TNBC is that the top of the recurrence is between the first and the third years and most of the deaths appear within the 5 years post treatment. After the appearance of the first metastatic tumor, patients with TNBC have a shorter survival rate compared with patients with non TNBC (6, 9, 11). There is a weak association between the tumor size and the node involvement, in other words, even size small tumors have a high frequency of lymph node involvement (11). TNBC is more likely to metastasize in central nervous system, lung and liver (11, 12).The prognosis of the disease is inferior compared to non-TNBC. In the TNBC (6) type of cancer, the survival, and the probability of distant reappearing and death are specific to be at a high rate. Due to the fact that TNBC has 0 response to to endocrine or HER2 therapy, the principal and the most effective treatment is chemotherapy. A characteristic of these tumors is their chemosensitivity despite their poor outcome. A combination of anthracyclines and taxanes (11,13,14) represents the main treatment in this cases. Their efficacy was proven even in metastatic disease although, in this case, there are some limitations of these regimens: these drugs are usually used in adjuvant therapy, the disease- free interval is short and the maximum anthracyclines doses have cardiotoxicity, thus questioning the chemosensitivity to these drugs (11).Two neoadjuvant studies analyzed the relation between chemosensitivity and outcome in breast cancers (15,16). In both studies patients with a pathologic complete response had a good prognosis regardless of subtype. The women with higher risk of recurrence were those with a residual response after neoadjuvant therapy. What it is important to remember is that there are patients with TNBC who are well treated with common chemotherapy, but this subtype requires more research and more effective therapies capable of dealing with the disease (15,16). A higher response rate was observed in the chemotherapy treatment for TNBC, compared to the luminal A or B, on the other side, this subtype suffers from a shorter disease-free period and overall survival (17). Multiple studies for TNBC with BRCA1 mutations conclude with that the platinum salt agents should be added in chemotherapy. Their mechanism of action is that they cause DNA cross-link stand breaks and they can be effective in cells with BRCA mutants because of their dysfunction in repair mechanism (13,14,17). The recommendations for BRCA testing should be offered to all patients with TNBC under 40 (13). Antiangiogenic agents, EGFR inhibitors and PARP inhibitors, are also targeted against TNBC, and are now taken into considerations while scientific endeavors are determined to discover newer and better solutions. The antiangiogenic agents, such as Bevacizumab (Avastin) are analyzed in approaching TNBC. High VEGF 2 expression has been observed in the subgroup of TNBC (12). Bevacizumab is a monoclonal antibody that targets all forms of vascular endothelial growth factor (VEGF) that was approved by the FDA as first-line treatment for metastatic breast cancer (11). The TNBC patients showed a clear advantage in terms of response rates and time to progression with the addition of the Bevacizumab (11). Now, there are studies that analyze the use of Bevacizumab in adjuvant and neoadjuvant chemotherapy in only TNBC (11). Other small-molecule kinase inhibitors, including sunitinib and sorafenib, have been developed as potential antiangiogenic agents and are under investigation for the treatment of TNBC (11,12). Some investigations for the treatment of the TNBC are undertaken in relation to some EGFR inhibitors, such as Cetuximab (Erbitux) (6, 11). The inhibitors are supposed to be responsible for a series of adverse effects such as fatigue, diarrhea and vomiting, neutropenia and thrombocytopenia (6).Assessment the role of the BRCA 1 in breast cancer and identifying the metabolic pathways has led to the progression of new therapeutic options. We need to discover better biological characterization of TNBC in order to develop specific therapies for each subgroup. Conclusions In conclusion, TNBC represents a clinical challenge because of its unique characteristics, from the perspective of molecular, biological and clinical features, prognosis and therapeutic options. The importance of chemotherapy in dealing with the disease has led to new clinical trials that investigate new strategies in understanding and treatment of the challenging TNBC