Molecular Classification and Future Therapeutic Challenges of Triple-negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is an extremely diverse group of breast tumors, with aggressive clinical behavior, higher rates of distant recurrence and worse overall survival compared to other types of breast cancers. The genetic, transcriptional histological and clinical heterogeneity of this disease has been an obstacle in the progression of targeted therapeutic approaches, as a ubiquitous TNBC marker has not yet been discerned. In terms of that, current studies focus on the classification of TNBC tumors in subgroups with similar characteristics in order to develop a treatment specialized for each group of patients. To date, a series of gene expression profiles analysis in order to identify the different molecular subtypes have been used. Complementary DNA microarrays, PAM50 assays, DNA and RNA sequencing as well as immunohistochemical analysis are some of the methods utilized to classify TNBC tumors. In 2012, the Cancer Genome Atlas (TCGA) Research Network conducted a major analysis of breast cancers using six different platforms, the genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays, in order to assort the tumors in homogenous subgroups. Since then, an increasing number of breast cancer data sets are being examined in an attempt to distinguish the classification with biological interpretation and clinical implementation. In this review, the progress in molecular subtyping of TNBC is discussed, providing a brief insight in novel TNBC biomarkers and therapeutic strategies.

Triptonide Effectively Inhibits Triple-Negative Breast Cancer Metastasis Through Concurrent Degradation Of Twist1 And Notch1 Oncoproteins

“…The initiation and metastasis of TNBC are driven by the overexpression of numerous oncogenic genes and aberrant activation of multiple tumorigenic signaling pathways [6][7][8][9][10]. Despite decades of research, druggable targets for TNBC have been di cult to identify [3,5,12,56], which has hindered the development of effective therapeutics for the disease. In the current study, we explored the ability of an active compound to inhibit TNBC cell tumorigenesis and dissemination in vitro and in vivo.…”

Cáncer de mama triple negativo: terapias sistémicas actuales y experiencia local

“…del factor de crecimiento epidérmico humano tipo 1 (EGFR 1) 10 . La determinación de su perfil molecular intrínseco ha distinguido más grupos; algunos con un patrón similar a tumores hormono-dependientes y otros que expresan el receptor de andrógenos, por ejemplo.…”

“…La determinación de su perfil molecular intrínseco ha distinguido más grupos; algunos con un patrón similar a tumores hormono-dependientes y otros que expresan el receptor de andrógenos, por ejemplo. No obstante, esta clasificación por subtipos moleculares aún no es aplicable enteramente a la práctica clínica en nuestra realidad, al no tener un correlato terapéutico definido y reservado por ahora, en muchos casos, a su aplicación en ensayos clínicos (Tabla 2) 10,11 . Para entender y contextualizar el desarrollo de terapias moleculares recientes en CMTN, revisaremos algunos aspectos generales de biomarcadores asociados a su clasificación y respuesta a terapias sistémicas.…”

UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology

“…ERbreast cancers are more aggressive than ER+ breast cancers [7], and TNBCs are the most aggressive sub-type and also very difficult to treat due to their lack of ER, progesterone receptor and HER2 expression. Metastatic ER− and triple-negative breast cancers have very limited treatment options available and are a leading cause of cancer-related death in women [8][9][10][11][12]. Thus understanding the mechanisms of ER regulation in breast cancers is critical for developing effective therapeutic strategies for their treatment.…”