Clinical significance of HER2-low expression in early breast cancer: A single-center experience

Background: Human epidermal growth factor receptor 2-low (HER2-low) breast cancer has recently been recognized as a subgroup of HER2-negative disease, but its significance in early-stage cases, especially in lower-income countries where newer treatments are not available, is still unclear. Methods: We reviewed the data of 535 patients with early-stage breast cancer treated between January 2020 and December 2021 at a single hospital. HER2 status was classified as either HER2-negative (immunohistochemistry [IHC] 0) or HER2-low (IHC 1+ or 2+/ISH-negative). For each patient, we collected clinicopathological details, treatment received, and survival outcomes. Disease-free survival and overall survival were calculated using the Kaplan–Meier method, and Cox regression was used to analyze which factors influenced prognosis. Results: Of the 535 patients, 37.6% had HER2-low tumors and 62.4% had HER2-zero tumors. HER2-low cancers were more likely to be hormone receptor–positive. After following patients for about 3 years, no significant differences in disease-free survival (log-rank p = 0.297) or overall survival (log-rank p = 0.479) were observed between the 2 groups. Multivariate analysis showed that lymph node status was the strongest predictor of recurrence, and the HER2-low status itself had no independent association with survival. Among patients with positive lymph node involvement, those with HER2-low tumors appeared to perform slightly better; however, this was not statistically significant. Conclusions: HER2-low expression does not confer a survival advantage in the early stages of breast cancer. At present, HER2-low is not a solid prognostic marker. Larger prospective studies with standardized HER2 testing and molecular profiling are needed.