Work

Prognostic difference between early breast cancer patients with HER2 low and HER2 zero status

Year: 2025

Type: article

Abstract: Background Since the approval of the trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)-low breast cancer, evidence suggests that low-HER2 expression may affect prognosis; however, it remains unclear how HER2-low subtype affects outcomes. Thus, this study aimed to investigate the differences in prognosis between patients with HER2-low and HER2-zero status. Methods This retrospective cohort study conducted at multi-institution included 1,627 patients diagnosed with HER2-low or HER2-zero breast cancer (stages I–III). For comparing outcomes between two groups, the survival analysis after propensity score matching was used. Survival outcomes including distant recurrence-free survival, and overall survival were evaluated using the Kaplan–Meier analyses. Results After propensity score matching, 445 patients with HER2-low and 707 patients with HER2-zero status were included. Among them, 914 (79.3%) and 238 (20.7%) patients had hormone receptor-positive and -negative disease. Median follow-up was 92.7 months. Locoregional recurrence-free survival and distant recurrence-free survival were comparable between patients with HER2-low and HER2-zero status (p = 0.872, p = 0.746, respectively). HER2-low status did not affect overall survival. However, in a subgroup with lymph node metastases, patients with HER2-low status showed better recurrence-free survival compared with that of patients with HER2-zero status (p = 0.033). Conclusions In this study, survival outcomes were comparable between patients with HER2-low and HER2-zero breast cancer. Additionally, patients with HER2-low status showed better survival outcomes compared with those with HER2-zero in the subgroup with lymph node metastasis. Further studies are needed to examine the biological mechanism underlying these prognostic differences.

Source: npj Breast Cancer

DOI: 10.1038/s41523-025-00737-8