AUTHOR=Godoy-Ortiz Ana , Sanchez-Muñoz Alfonso , Chica Parrado Maria Rosario , Álvarez Martina , Ribelles Nuria , Rueda Dominguez Antonio , Alba Emilio 

TITLE=Deciphering HER2 Breast Cancer Disease: Biological and Clinical Implications

JOURNAL=Frontiers in Oncology

VOLUME=Volume 9 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01124

DOI=10.3389/fonc.2019.01124

ISSN=2234-943X

ABSTRACT=The identification of extensive genetic heterogeneity in human breast carcinomas poses a significant challenge for designing effective treatment regimens. Significant genomic evolution often occurs during breast cancer progression, creating variability within primary tumors as well as between the primary carcinoma and metastases. A clear example of this is the HER2 positive breast cancer. The clinical impact of the biological heterogeneity within HER2-positive breast cancer is not fully understood. In these tumors, we can find all of the transcriptional subtypes of breast cancer, even the basal like or luminal A subtypes. While the HER2-enriched subtype is the most representative transcriptional subtype in this tumor, we can find it too in HER2-negative breast cancers. This subtype is characterized by high expression of the HER2 and proliferation gene clusters. Thus, the following hypothesis can be suggested: the HER2 amplification can be a distinct driver event seen in all intrinsic subtypes, rather than a subtype marker, and the HER2-enriched subtype can have a distinctive transcriptional landscape independent of HER2 amplification. In this review, we present an extensive revision about the last highlights and advances in clinical outcomes and genomic features in the HER2-positive breast cancer and the HER2-enriched subtype, in an attempt to improve understanding the underlying biology and the drivers of both entities.