biostudies-literatureMerlin JLSeagen3164https://www.ebi.ac.uk/biostudies/studies/S-EPMC10740754biostudies-literatureUnknown11(12)Based on immunohistochemistry (IHC) and in situ hybridization (ISH), HER2-low breast cancers (BC) subtype-defined as IHC1+ or IHC2+/ISH- tumors-emerged and represent more than half of all BC. We evaluated the performance of NGS for integrated molecular characterization of HER2-low BC, including identification of actionable molecular targets, copy number variation (CNV), and microsatellite instability (MSI) analysis. Thirty-one BC specimens (11 HER2+, 10 HER2-, and 10 HER2-low) were routinely analyzed using IHC and ISH, and were selected and analyzed using NGS for gene mutations including <i>ESR1</i>, <i>PIK3CA</i>, <i>AKT1</i>, <i>ERBB2</i>, <i>TP53</i>, <i>BRCA1</i>, and <i>BRCA2</i>, CNV, and MSI. CNV values for the <i>ERBB2</i> gene were significantly (<i>p</i> < 0.001) different betweeBiomedicinesIntegrated Molecular Characterization of HER2-Low Breast Cancer Using Next Generation Sequencing (NGS).PMC10740754FR-GD/2022/001Leroux ASahki NMerlin JLMassard VHusson MHarle AGilson PfalseIntegrated Molecular Characterization of HER2-Low Breast Cancer Using Next Generation Sequencing (NGS).Based on immunohistochemistry (IHC) and in situ hybridization (ISH), HER2-low breast cancers (BC) subtype-defined as IHC1+ or IHC2+/ISH- tumors-emerged and represent more than half of all BC. We evaluated the performance of NGS for integrated molecular characterization of HER2-low BC, including identification of actionable molecular targets, copy number variation (CNV), and microsatellite instability (MSI) analysis. Thirty-one BC specimens (11 HER2+, 10 HER2-, and 10 HER2-low) were routinely analyzed using IHC and ISH, and were selected and analyzed using NGS for gene mutations including <i>ESR1</i>, <i>PIK3CA</i>, <i>AKT1</i>, <i>ERBB2</i>, <i>TP53</i>, <i>BRCA1</i>, and <i>BRCA2</i>, CNV, and MSI. CNV values for the <i>ERBB2</i> gene were significantly (<i>p</i> < 0.001) different betwee2023-01-01T00:00:00Z2023 Nov2025-05-18T13:06:33.784Z2025-05-18T13:06:33.784ZS-EPMC107407543813738510.3390/biomedicines11123164