Molecular characteristics and prognosis of triple negative breast cancer stratified by HER2 status

Human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) is an emerging subtype with specific clinicopathological features and therapeutic strategies. However, limited studies are available on the molecular characteristics and prognosis of triple-negative breast cancer (TNBC).

This study was conducted using the clinicopathological and genomic data of 1006 TNBC patients, which were extracted from The Cancer Genome Atlas (TCGA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), and Sir Run Run Shaw Hospital of Zhejiang University (SRRSH) cohorts. The clinicopathological features, survival outcomes, molecular characteristics, and immune profiles of TNBCs based on HER2 status were evaluated.

Patients were stratified into HER2-low ( N = 676) and HER2-zero ( N = 330) groups according to their HER2 status. We found HER2-low TNBCs had a lower histological grade and Ki67 index compared to the HER2-zero subgroup in the SRRSH cohort. However, no significant association has been found between the HER2 status and the disease-free survival (DFS), recurrence-free survival (RFS), or overall survival (OS) in TNBCs. Genomic mutation analysis showed that the HER2-low TNBCs exhibited higher mutated frequencies of PIK3CA, MUC17 , and PTEN , while FAT3, RYR2 , and CSMD3 were more frequently mutated in the HER2-zero subgroup. Furthermore, the combined mutation of PIK3CA and MUC17 , which had a higher frequency in the HER2-low subgroup, was associated with poorer survival in TNBCs. Immune profile analysis revealed a higher percentage of plasma cells in patients with low HER2 expression.

Taken together, our study reflected the impact of the HER2 status on the clinicopathological and molecular features of TNBCs, which might offer additional introspection and improvement for translational studies and therapeutic decisions for TNBCs.