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Updated: Sep 9, 2025

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Comparison of clinical characteristics and survival between HER2-zero and HER2-low in early breast cancer: a
Violeta Núñez Álvarez1,2, Belén González Castilla1,2, Belén Fernández Rivero1,2
1Servicio de Oncología Médica (Medical Oncology Department), Hospital Universitario Puerta del Mar, Avenida de Ana de Viya 21, 11009, Cádiz, Spain.
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.
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