Integrated Molecular Characterization of HER2-Low Breast Cancer Using Next Generation Sequencing (NGS)

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• HER2-low breast cancer (BC), defined by immunohistochemistry (IHC) and in situ hybridization (ISH), constitutes over half of all BC cases.
• Accurate molecular subtyping is crucial for effective treatment strategies in BC.

Purpose of the Study:

• To evaluate the performance of next-generation sequencing (NGS) for comprehensive molecular characterization of HER2-low BC.
• To assess NGS's ability to identify actionable molecular targets, copy number variations (CNV), and microsatellite instability (MSI).

Main Methods:

• Thirty-one BC specimens (HER2+, HER2-, HER2-low) were analyzed using IHC, ISH, and NGS.
• NGS was employed for gene mutation analysis (e.g., ESR1, PIK3CA, ERBB2), CNV, and MSI detection.

Main Results:

• NGS achieved 96.8% concordance with IHC/ISH for HER2 status determination.
• Gene mutations and amplifications were identified in 68% and 19% of cases, respectively.
• Significant differences in ERBB2 gene CNV were observed between HER2+ and HER2-low/HER2- tumors (p < 0.001).

Conclusions:

• NGS provides integrated molecular profiling of HER2-low BC, complementing IHC/ISH.
• NGS facilitates the simultaneous identification of HER2 status and actionable mutations, aiding molecular board treatment selection.