Deciphering HER2 Breast Cancer Disease: Biological and Clinical Implications

Abstract

The main obstacle for designing effective treatment approaches in breast cancer is the extensive and the characteristic heterogeneity of this tumor. The vast majority of critical genomic changes occurs during breast cancer progression, creating a significant variability within primary tumors as well as between the primary breast cancer and their metastases, a hypothesis have already demonstrated in retrospective studies (1). A clear example of this is the HER2-positive breast cancer. In these tumors, we can find all of the transcriptional subtypes of breast cancer, even the basal like or luminal A subtypes. Although the HER2-enriched is the most representative transcriptional subtype in the HER2-positive breast cancer, we can find it too in breast cancers with HER2-negative status. This intrinsic subtype shows a high expression of the HER2 and is associated with proliferation-related genes clusters, among other features. Therefore, two hypotheses can be suggested. First, the HER2 amplification can be a well-defined driver event present in all of the intrinsic subtypes, and not a subtype marker isolated. Secondly, 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 and genomic settings of the HER2-positive breast cancer and the HER2-enriched subtype, in an attempt to improving the knowledge of the underlying biology of both entities and to explaining the intrinsic heterogeneity of HER2-positive breast cancers.

<p>Association Between the HER2 Protein Expression Level and the Efficacy of Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer</p>

“…The overexpression and/or amplification of HER2 is not only correlated with disease progression and poor prognosis but also the only biomarker to decide anti-HER2 therapy. 10 The emergence of trastuzumab has significantly improved the prognosis of patients with HER2-positive breast cancer, 11 However, no apparent clinical benefit has been achieved in a considerable proportion of patients. The heterogeneity of HER2 protein expression and its predictive value for prognosis and neoadjuvant efficacy have received attention.…”

Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

“…A subset of HER2 + breast carcinomas may also express steroid receptors: estrogen (ER) and progesterone (PR) receptors (Luminal B tumors). These tumors appear to be clinically less aggressive than HER2 + breast cancers and are associated with a better prognosis [9].…”

UCNP-based Photoluminescent Nanomedicines for Targeted Imaging and Theranostics of Cancer

“…One of the most significant tumor markers is HER2, a human epidermal growth factor receptor, overexpression is directly related to the growth of various types of malignant tumors (breast and cervix adenocarcinoma, ovary and lung carcinoma, etc.) [ 20 ] and indicates their aggressiveness and high metastatic potential [ 29 , 30 , 31 ]. Therefore, the creation of HER2-specific complexes is an actual direction in diagnostics and therapy.…”