Clinicopathological Outcomes of Preoperative Chemotherapy in Patients with HER2-Low Versus HER2-Zero Breast Cancer: A Retrospective Cohort

Abstract

Background: Re-evaluating the binary classification of HER2 expression, shifting it from a simple negative or positive classification into an intermediate spectrum, has become mandatory with the evolution of anti-HER2 targeting agents. Ongoing trials have been focusing on HER2-low status and its influence on disease phenotype, prognostic value, and whether sufficient data exists to recognize this subgroup as a distinct entity. This research aims to evaluate the clinicopathological characteristics and their impact on prognosis in breast cancer patients expressing HER2-low and HER2-zero levels who received preoperative chemotherapy.Methods: Our study involved a retrospective analysis of 100 patients staged I–III invasive breast cancer treated with preoperative chemotherapy. All participants subsequently received surgical excision, followed by appropriate adjuvant therapy. Classification into HER2-low (IHC 1+ or 2+ with negative ISH) and HER2-zero (IHC 0) subgroups was performed based on immunohistochemical and in situ hybridization assessments.Clinicopathological variables were evaluated, such as tumor size, lymph node involvement, hormone receptor expression, tumor grade, and Ki-67 proliferation index. Additionally, treatment outcomes—including pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS)—were thoroughly assessed.Results: 58 patients of our cohort had HER2-zero expression, while 42 were HER2-low. The HER2-low subgroup demonstrated a markedly higher rate of hormone receptor positivity (100% compared to 36%). The total pathological complete response (pCR) rate reached 12%, with a statistically significant variation observed between the HER2-low and HER2-zero groups (p = 0.002). Disease-free survival was significantly lower in HER2-low individuals than in HER2-zero ones (p = 0.001), while overall survival showed no statistical difference.Conclusion: Compared to HER2-zero cases, patients with HER2-low breast cancer demonstrated distinct clinicopathological characteristics and showed a less favorable response to preoperative chemotherapy along with shorter disease-free survival, pressing the need for tailored therapeutic strategies.