HER2 IHC score as a predictor of pathologic complete response in HER2-positive breast cancer after neoadjuvant therapy

Abstract

Aim: To evaluate factors associated with pathologic complete response (pCR) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant therapy, with a specific focus on the prognostic relevance of HER2 immunohistochemistry (IHC) scores.

Materials and Methods: This retrospective study included 147 patients with HER2-positive breast cancer who underwent neoadjuvant chemotherapy (NAC) followed by surgery at a tertiary care center from late 2022 to 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-negative status (p=0.037) as independent predictors of achieving pCR.

Conclusion: Positivity for estrogen and progesterone receptors was more prevalent in the IHC 2+/ISH+ group than in the IHC 3+ group. HER2 IHC 3+ status and progesterone receptor negativity were identified as independent predictors of pCR.