Related Experiment Video
Updated: Nov 23, 2025
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer
Francesco Schettini1,2,3, Nuria Chic2,3,4, Fara Brasó-Maristany2,4
1Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Abstract:
Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.
Insights
HER2-low breast cancer (BC) shows significant biological heterogeneity. Further research is needed to develop reproducible assays for measuring low HER2 expression in BC patients.
Area of Science:
- Oncology
- Genomics
- Pathology
Background:
- Novel antibody-drug conjugates targeting HER2 demonstrate efficacy in HER2-low breast cancer (BC).
- The clinical and molecular characteristics of HER2-low BC remain largely undefined.
- HER2-low BC is defined as HER2 1+ or 2+ without ERBB2 amplification.
Purpose of the Study:
- To elucidate the clinical and molecular features of HER2-low breast cancer.
- To compare HER2-low characteristics between hormone receptor-positive (HR-positive) and triple-negative breast cancer (TNBC).
- To assess the association of HER2-low status with overall survival and evaluate the reproducibility of HER2 assessment.
Main Methods:
- Retrospective collection of clinicopathological and PAM50 gene expression data from 3,689 HER2-negative BC patients.
- Analysis of HER2 expression levels, gene expression profiles, and overall survival data.
- Evaluation of inter-pathologist reproducibility for HER2 scoring.
Main Results:
- HER2-low BC was more prevalent in HR-positive disease (65.4%) than in TNBC (36.6%).
- In HR-positive BC, HER2-low tumors showed higher ERBB2 and luminal gene expression compared to HER2 0 tumors.
- No differential gene expression was observed in TNBC based on HER2 expression levels.
- ERBB2 levels were higher in HER2-low HR-positive BC compared to HER2-low TNBC.
- HER2-low status was not significantly associated with overall survival in either HR-positive BC or TNBC.
- Pathologist agreement on HER2-low status was suboptimal.
Conclusions:
- HER2-low breast cancer exhibits substantial biological heterogeneity.
- The findings highlight the need for standardized, sensitive, and reproducible assays for assessing low HER2 expression in BC.
- Further investigation is warranted to refine diagnostic criteria and therapeutic strategies for HER2-low BC.
More Related Videos
06:06High-Throughput Dissociation and Orthotopic Implantation of Breast Cancer Patient-Derived Xenografts
Published on: December 20, 2024
11:34Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
