Comparison of clinical characteristics and survival between HER2-zero and HER2-low in early breast cancer: a retrospective observational study.

Purpose: Human epidermal growth factor receptor 2 (HER2)-negative breast cancer includes HER2-zero and HER2-low tumors. Whether their clinical features and survival are different is not fully clarified. The objective was to explore their clinicopathologic differences and survival.

Methods/patients: Retrospective analysis of HER2-negative, stage I-III breast cancer patients from 2006 to 2016 at a single site. Clinicopathological variables, events and survival are analyzed, comparing HER2-low and HER2-zero cases.

Results: Of 535 patients, 351 (65.61%) were HER2-zero and 184 (34.39%) HER2-low (154 (83.70%) score 1 + and 30 (16.30%) score 2 +). The proportion of premenopausal women was higher in the HER2-low subgroup (50.50% vs 39.40%, p = 0.016). For those with HER2-zero tumors, 15.70% were estrogen receptor (ER) negative, whereas only 9.20% (p = 0.045) of HER2-low tumors were ER negative. In HER2-low/ER negative tumors, tumor size, histologic grade, and Ki67 levels were higher. Patients with HER2-zero/ER-negative tumors were younger, had fewer comorbidities, less nodal involvement, a higher frequency of ductal histopathology, and, again, higher histologic grade and Ki67 levels. There were no differences in the events. The overall survival probability at 11.50 years in the HER2-zero subgroup was 0.51 (95% confidence interval (CI 95%) 0.28-0.74) and in the HER2-low subgroup 0.67 (95% CI 0.56-0.77) (p = 0.52).

Conclusions: HER2-zero and HER2-low breast cancers are not distinct clinicopathologic entities. The differences detected in some variables seem to depend on ER status. No prognostic differences were observed.