AimsThis study aimed to investigate whether the efficacy of neoadjuvant chemotherapy differs between HER2-low and HER2-zero subgroups in hormone receptor-positive, HER2-negative breast cancer.Materials and MethodsA total of 61 patients who received neoadjuvant chemotherapy between 2015 and 2025 were retrospectively analyzed. HER2 status was determined from pre-treatment core biopsy specimens and classified as HER2-low (IHC 1 + or 2 + and FISH-negative) or HER2-zero (IHC 0). The pathological complete response (pCR) rates were compared between the two groups.ResultsAmong 61 patients, 28 had HER2-low and 33 had HER2-zero tumors. The pCR rate was 7.1% in the HER2-low group and 27.3% in the HER2-zero group (p = 0.042). A post-hoc power analysis based on these results showed a moderate power (0.59) to detect the observed difference.ConclusionsHER2-low expression may negatively influence chemosensitivity in hormone receptor-positive breast cancer treated with neoadjuvant chemotherapy. Further studies are warranted to evaluate the potential role of trastuzumab deruxtecan (T-DXd) and other antibody-drug conjugates in this newly defined subgroup.
Mustafa Ersoy (Sun,) studied this question.