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Updated: May 27, 2026
Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
Clinicopathological Characterization of HER2-Low-Expressing Triple-Negative Breast Cancer: Distinct Features From
Michiko Kato1, Hiroko Masuda2, Sayuka Nakayama3
1Department of Surgery, Division of Breast Surgical Oncology, Showa Medical University, Shinagawa-ku, Tokyo, Japan; Department of Pathology, Showa Medical University, Shinagawa-ku, Tokyo, Japan.
Background:
Triple-negative breast cancer (TNBC) is an aggressive disease characterized by a poor prognosis and marked biological heterogeneity. Recently, HER2-low tumors have emerged as potential therapeutic targets. However, the clinical and biological significance of HER2-low TNBC remains unclear.
Methods:
We retrospectively analyzed 195 patients with primary TNBC treated at our institution between April 2014 and May 2023. Clinicopathological data, including histological subtype, androgen receptor (AR) expression, BRCA mutation status, Ki-67 index, epidermal growth factor receptor, CK5/6, nuclear grade, and treatment response, were collected. Tumor-infiltrating lymphocytes (TILs) and programmed cell death 1 ligand 1 (PD-L1) expression were assessed in available biopsy samples. Patients were classified into HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+ and fluorescence in situ hybridization negative) and HER2-zero (IHC 0) groups.
Results:
Among the 195 TNBC cases, 74 (38%) were HER2-low and 121 (62%) were HER2-zero. HER2-low tumors showed higher rates of apocrine carcinoma (32% vs. 15%) and AR positivity (47% vs. 21%). Conversely, HER2-zero tumors exhibited a higher prevalence of BRCA mutations (36% vs. 15%), elevated Ki-67 expression (69% vs. 54%), and increased PD-L1 positivity (63% vs. 44%). TILs correlated with PD-L1, but not with HER2 status. The pathological complete response rates after neoadjuvant chemotherapy were similar between groups.
Conclusion:
HER2-low and HER2-zero TNBC are biologically distinct subgroups. HER2-low tumors are enriched in luminal AR-like characteristics, whereas HER2-zero tumors exhibit basal-like, highly proliferative, and immunogenic features. Although the treatment outcomes did not differ significantly, these findings suggest that HER2-low and HER2-zero TNBC may require different therapeutic approaches. Prospective studies are warranted to validate these findings and further explore tailored treatment strategies.
