HER2 gene mutations and matrix biomarkers in breast cancer

Breast cancer (BC) remains a leading cause of morbidity and mortality among women globally. This study aims to investigate HER2 mutations in HER2-negative BC and evaluate the diagnostic potential of matrix metalloproteinases (MMP-7, MMP-9) and CYR61 as serum biomarkers.

The study involved 74 women diagnosed with BC (HER2-positive: n = 33; HER2-negative: n = 33; triple negative: n = 8) and 25 healthy controls. HER2 gene mutations were analyzed using the "AmoyDx HER2 Mutation Detection" kit. Serum MMP-7, MMP-9, and CYR61 levels were quantified using Bio-Techne kits (R&D Systems) using the Quantikine ELISA method.

The study found no mutations (A775_G776insYVMA, M774_A775insAYVM, G776 > VC, G776R, G776C, P780_Y781insGSP, V777L, L755P) in exons 18 and 20 of the HER2 gene in HER2 negative BC patients. MMP-9 serum levels were significantly reduced in BC patients compared to the control group (p < 0.001). However, MMP-7 levels showed no significant variation when compared to healthy women (p = 0.464). CYR61 exhibited high diagnostic accuracy (AUC = 0.95), supporting its potential as a reliable biomarker.

The reduction in serum MMP-9 levels correlates with ongoing tissue processes, primarily due to increased consumption in the extracellular matrix. CYR61 overexpression is observed across all breast cancer subtypes, independent of HER2 activity, suggesting its significant potential for use in BC diagnosis and treatment.