Clinical Significance of HER2-low Expression in Triple-negative Breast Cancer: A Retrospective Multicenter Study

The clinical significance of human epidermal growth factor receptor 2 (HER2)-low expression in triple-negative breast cancer (TNBC) remains unclear. Although the emergence of antibody-drug conjugates has drawn attention to HER2-low tumors, whether HER2-low represents a biologically distinct subtype within TNBC is still under investigation.

We retrospectively analyzed 261 patients with TNBC who underwent neoadjuvant chemotherapy followed by curative surgery at four institutions between 2008 and 2018. Clinicopathological features, chemotherapy effect, and patient outcomes were compared between HER2-low and HER2-null groups.

No significant differences were observed in pathological complete response rates or survival outcomes between the HER2-low and HER2-null groups. However, compared to HER2-low tumors, HER2-null tumors showed a significantly higher Ki67 labeling index (p=0.004), a trend toward higher pathological complete response rates, and a tendency for worse distant metastasis-free survival (p=0.401).

Although the HER2-low and HER2-null tumor groups among TNBC showed no significant differences in response to neoadjuvant chemotherapy or patient outcomes, the higher proliferative activity and differing outcome trends in HER2-null tumors suggest possible biological differences.