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Front. Oncol. | doi: 10.3389/fonc.2019.01124

Deciphering HER2 breast cancer disease: biological and clinical implications

 Ana G. Ortiz1, 2*, Alfonso S. Muñoz1, 3,  Maria Rosario C. Parrado2,  Martina Á. Pérez2, 3, Nuria R. Entrena4, Antonio R. Dominguez1, 2 and  Emilio A. Conejo2, 3, 4, 5, 6
  • 1Regional University Hospital of Malaga, Spain
  • 2Laboratory of Molecular Biology of Cancer, Medical-Health Research Center, University of Malaga, Spain
  • 3Faculty of Medicine, University of Malaga, Spain
  • 4Hospital Clínico Universitario Virgen de la Victoria, Spain
  • 5Spanish Breast Cancer Group, Spain
  • 6Center for Biomedical Research in Cancer Network (CIBERONC), Spain

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.

Keywords: breast cancer, heterogeneity, Intrinsic subtype, Molecular diagnosis, Oncodrivers

Received: 16 Jun 2019; Accepted: 09 Oct 2019.

Copyright: © 2019 Ortiz, Muñoz, Parrado, Pérez, Entrena, Dominguez and Conejo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ana G. Ortiz, Regional University Hospital of Malaga, Málaga, Andalusia, Spain,