HER2 IHC Score as a Predictor of Pathologic Complete Response in HER2-Positive Breast Cancer After Neoadjuvant Therapy

Abstract

Aim: This study aims to evaluate the factors associated with pathologic complete response (pCR) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients receiving neoadjuvant therapy, with a specific focus on the prognostic relevance of HER2 immunohistochemistry (IHC) scores. Methods: This retrospective study included 147 HER2-positive breast cancer patients who received neoadjuvant chemotherapy (NAC) followed by surgery at a tertiary care center between late 2022 and early 2025. Patients were categorized into two groups based on their HER2 IHC status: IHC 2+/in situ hybridization-positive (ISH+) and IHC 3+. We compared patients\' clinicopathological features and pCR rates. pCR was defined as the absence of residual invasive carcinoma in the breast and axillary lymph nodes (ypT0/is ypN0). Results: The overall pCR rate was 54% (n = 79). Among patients with HER2 IHC 3+ tumors, pCR was achieved in 73 of 121 cases (60%), compared with 6 of 26 cases (23%) in the IHC 2+/ISH+ group (p < 0.001). In univariate analyses, HER2 IHC score (IHC 2+/ISH+ vs IHC 3+) (p < 0.001), estrogen receptor negativity (p < 0.001), and progesterone receptor negativity (p < 0.001) were significantly associated with pCR. Multivariate analysis identified HER2 IHC 3+ status (p = 0.035) and progesterone receptor negativity (p = 0.037) as independent predictors of achieving pCR. Conclusions: Estrogen and progesterone receptor positivity were more prevalent in the IHC 2+/ISH+ group compared to the IHC 3+ group. HER2 IHC 3+ status and progesterone receptor negativity were identified as independent predictors of pCR