Triple-negative breast cancer: are we making headway at least?

Abstract

Abstract:The so-called triple-negative breast cancer, as defined by tumors that lack estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) overexpression, has generated growing interest in recent years despite representing less than 20% of all breast cancers. These tumors constitute an important clinical challenge, as they do not respond to endocrine treatment and other targeted therapies. As a group they harbor an aggressive clinical phenotype with early development of visceral metastases and a poor long-term prognosis. While chemotherapy remains effective in triple-negative disease, research continues to further identify potential new targets based on phenotypical and molecular characteristics of these tumors. In this respect, the presence of a higher expression of different biomarkers including epidermal growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptor and Akt activation has led to a proliferation of clinical trials assessing the role of inhibitors to these pathways in triple-negative tumors. Moreover, the described overlap between triple-negative and basal-like tumors, and the similarities with tumors arising in the BRCA1 mutation carriers has offered potential therapeutic avenues for patients with these cancers including poly (ADP-ribose) polymerase inhibitors and a focus on a higher sensitivity to alkylating chemotherapy agents. Results from these trials have shown some benefit in small subgroups of patients, even in single-agent therapy, which reflects the heterogeneity of triple-negative breast cancer and highlights the need for a further subclassification of these types of tumors for better prognosis identification and treatment individualization.

Novel c-Met inhibitory olive secoiridoid semisynthetic analogs for the control of invasive breast cancer

“…TNBC is characterized by a lack of the expression of the ER, progesterone receptor and HER-2 [43]. It accounts for about 17% of all breast cancers, representing an aggressive clinical behavior and is generally associated with poor prognosis; thus chemotherapy remains the only systemic treatment option available for these patients [43]. Accordingly, there is a need to develop new treatments for this aggressive subtype, which currently lack targeted therapy.…”

Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells

“…TNBC is associated with shortened disease-free interval post-surgery and post-adjuvant treatment and, ultimately, a shortened overall survival. [12][13][14][15] Furthermore, TNBCs are themselves a heterogeneous group within which the claudinlow subtype is associated with worst prognosis. 16 Compared to the overall prevalence of breast cancer, a limited number of reports have indicated exosomes and/or microvesicles to be of relevance in breast cancer.…”

Prospective study of cyclophosphamide, thiotepa, carboplatin combined with adoptive DC-CIK followed by metronomic cyclophosphamide therapy as salvage treatment for triple negative metastatic breast cancers patients (aged <45)

“…The molecular substudy of CALGB 9342 demonstrated that patients with TNBC had a shorter median survival with metastatic disease than non-TNBC patients (8.6 versus 12.8 months; p = 0.009) [19]. It has been suggested that they seem to respond to chemotherapy better than other types of breast cancer, but prognosis remains very poor, if treated by conventional chemotherapy [20,21]. There were some trials to deploy the clinical responses through different chemotherapeutic regimens in the settings of the neoadjuvant, adjuvant, metastatic in pursuing of obtaining reliable responses.…”