Understanding the biology of triple-negative breast cancer

Abstract

Greater understanding of the biology of triple-negative breast cancer (TNBC) is needed to discern the roughly 60% of node-negative patients who are already cured with locoregional therapy from the 40% who need adjuvant systemic therapy to be cured. Recent evidence suggests that patients with TNBC whose tumours have an activated immune response gene signature have a more favourable outcome than TNBC patients without this signature. For the group who needs additional systemic therapy, the challenge remains to choose the right systemic drug combination for the right TNBC sub-type. Significant heterogeneity exists within the TNBC class that is exemplified by differing chemotherapeutic sensitivity observed for some sub-types. This heterogeneity establishes the need for identifying differentiating molecular markers within the overall class of TNBC disease, which may help refine therapeutic management. In this review, we discuss some of these promising predictive molecular markers for tailoring therapy. In addition, several gene expression profiling and functional studies employing genetic screens that help to establish TNBC sub-groups with varying sensitivities to a variety of targeted therapies currently under clinical investigation are conferred. It is anticipated that a greater understanding of the biology of TNBC and its complex heterogeneity will reveal novel targets or identify markers around which clinical trials in molecularly well-defined sub-groups can be designed.

Predictive and Prognostic Role of Tumor-Infiltrating Lymphocytes for Early Breast Cancer According to Disease Subtypes: Sensitivity Analysis of Randomized Trials in Adjuvant and Neoadjuvant Setting

“…for hormonal therapies or HER2-targeted agents, cytotoxic chemotherapy remains the cornerstone of the current treatment strategies. Therefore, the lack of specific targeted agents and the poor outcome of patients with TNBC indicates that studies are needed to understand the biology of this subtype and to identify predictive biomarkers of response or resistance to specific treatments [36,37]. In this regard, the concept that TNBC includes a heterogeneous group of diseases with various biological and molecular characteristics determining different clinical outcome is constantly emerging [38].…”

Biological subtypes of breast cancer: Prognostic and therapeutic implications

“…Despite the wide diversity of the involved pathways, signaling molecules, such as the mitogen activated protein kinase (MAPK), PI3K, Akt and nuclear factor kappa B (NF-κB), are commonly deregulated as seen in other breast cancer subtypes. Other alterations such as cytoplasmic and nuclear accumulation of beta catenin were also observed in basallike cancers, being the marker suggested as a potential therapeutic target for this cancer [48] . Microarray and immunohistochemical analyses demonstrated that basal-like subtype constitute approximately three quarters of breast cancer 1 (BRCA1) gene related breast cancers.…”

Knockdown of TAZ modifies triple-negative breast cancer cell sensitivity to EGFR inhibitors by regulating YAP expression

“…Therefore, patients with TNBC cannot be treated with endocrine therapy or therapies targeted to HER2. As a group, they have a worse prognosis and tend to relapse early compared with other subtypes of breast cancers (4). Hence, there is a compelling need to find more effective treatments.…”