Traits, response to neoadjuvant therapy and prognostic analysis of HER2-low and HER2-zero breast cancer across different hormone receptor status

Since the introduction of therapies based on anti-human epidermal growth factor receptor 2 (HER2), researchers have increasingly focused on HER2-low breast cancer (BC). Here, we compared clinicopathological traits, response to treatment, and prognosis of BC categorized as HER2-low and HER2-zero under neoadjuvant chemotherapy (NAC) setting. We retrospectively examined data collected from 554 HER2-negative BC patients who were prospectively enrolled at two institutions between January 2015 and June 2023. HER2-negative BC was categorized into two types: HER2-low and HER2-zero. We compared clinicopathological traits, pathological complete response (pCR), and long-term survival of HER2-low and HER2-zero BC patients. ypT0/isN0 is defined as pathological complete response (pCR), meaning no invasive carcinoma is shown in axillary lymph nodes or breast, regardless of the presence of ductal carcinoma in situ. The median follow-up was 62 months, with 11 patients lost to follow-up. The HER2-low and HER2-zero BC groups comprised 313 and 241 patients, respectively. Hormone receptor (HR) status-based stratification revealed that 269 and 285 patients showed HR-positive (HR+) and HR-negative (HR–) BC, respectively. In subgroup analysis, statistic differences in clinical N stage and tumor grade were noted in HER2-low and HER2-zero BC patients in the HR+ cohort ( P = 0.011 and 0.036, respectively). Among HR– patients, clinical T stage of HER2-low and HER2-zero BC patients differed ( P = 0.022). In multivariate analysis, pCR did not correlate with HER2 status in HR + and HR– cohorts ( P = 0.608 and 0.938, respectively). Moreover, in HR + and HR– cohorts, HER2-low BC patients and HER2-zero BC patients had almost comparable 5-year overall survival (OS) and disease-free survival (DFS) rates (both P > 0.05). Patient survival (OS and DFS) and HER2 status showed no interaction in multivariate analysis (both P > 0.05). HER2-low BC exhibited distinct clinicopathological features compared to HER2-zero BC; this difference was also noted across HR status. However, these differences do not translate into effects on treatment response to NAC and patient prognosis.