HER3 Expression and PIK3CA Mutational Status Predict Pathological Response of Neoadjuvant Therapy in HER2-Positive Breast Cancer Patients.

The main purpose of this study is to explore the predictive value of human epidermal growth factor receptor 3 (HER3) expression level and PIK3CA mutation for the efficacy of neoadjuvant therapy in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. The clinicopathological data of HER2-positive non-specific invasive breast cancer patients who received neoadjuvant treatment in the Second Affiliated Hospital of Anhui Medical University from June 2017 to June 2024 were retrospectively analyzed. The correlation between HER3 expression level detected by immunohistochemistry and PIK3CA gene mutation detected by amplification refractory mutation system-polymerase chain reaction and pathological complete response (pCR) was analyzed. Among 51 patients, 29 (56.9%) had positive HER3 expression, 15 (29.4%) had PIK3CA mutation, and 19 (37.3%) had pCR. The expression level of HER3 was correlated with the pCR rate (χ2=7.905, p=0.019). The PIK3CA mutation status was not correlated with the pCR rate (χ2=0.140, p=0.708). The HER3 expression level combined with PIK3CA mutation status affected the pCR rate (p=0.036). Multivariable regression further identified HER3 positivity as an independent negative predictor of pCR (odds ratio, 0.08; 95% confidence interval, 0.01 to 0.50; p=0.008), underscoring its role in therapeutic resistance. HER3 expression may serve as a critical biomarker for guiding therapeutic strategies in HER2-positive breast cancer patients. The combinatorial effect of HER3 overexpression and PIK3CA mutations may exacerbate therapeutic resistance, while dual-targeted strategies against the HER3/phosphoinositide 3-kinase pathway could potentially improve clinical outcomes in treatment-resistant populations.