Comparison of Clinicopathological Features and Survival Outcomes Associated with HER2-Zero and HER2-Low Breast Cancers: A retrospective, Observational Study

Despite being classified as HER2-negative, HER2-zero and HER2-low subtypes are considered distinct entities due to their varying clinicopathological features and survival outcomes. This study was designed to evaluate the sociodemographic, clinical, survival and prognostic differences between HER2-zero and HER2-low patients who were evaluated as HER2 negative. This retrospective singlecenter study included patients with HER2-negative non-metastatic breast cancer between 2003 and 2022. Patients were analyzed in two groups as HER2-zero and HER2-low. Of 680 patients, 484 (71%) were included in the HER2-zero group and 196 (29%) in the HER2-low group. Statistically significant differences were found between the groups in terms of histopathologic subtyping (p< 0.001), ER (p< 0.001) and PR status (p= 0.005), and presence of lymphovascular invasion (p= 0.023). When survival results were analyzed according to HER2 status, overall survival and disease-free survival were not statistically different for all patients. This result was also supported in luminal A, luminal B and triple negative patients (p>0.050). HER-2 status was not observed as a factor affecting OS and DFS in univariant and multivariant analyses (p> 0.050). There were no clinically and pathologically significant differences between HER2-low and HER2-zero, except that HER2-low patients had more ER and PR positivity, more luminal subgroups and more lymphovascular invasion. When evaluated together with histopathologic subgroups, no survival difference was detected between both groups. HER2 status could not be determined as a prognostic factor. Keywords: Breast cancer, Epidermal growth factor receptor, Survival analysis, Overall, Disease-free survival