Molecular Landscape, Genomic Shift, and Prediction in the Neoadjuvant Setting of Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

The amplification or overexpression of human epidermal growth factor receptor 2 (HER2) defines a breast cancer subtype, which benefits from neoadjuvant HER2-targeted therapy. However, at least 40% of patients respond poorly or do not respond to treatment. We analyzed the main genomic alterations of 64 HER2+ patients by next-generation sequencing to identify new predictors of response and correlate them with clinicopathological parameters. We also compared the genomic alterations between primary and residual tumors after neoadjuvant treatment. The TP53 gene was the most frequently mutated gene, and in combination with ERBB2 overexpression, the 2 were predictive of residual cancer burden (P = .001). Furthermore, the combination of their immunohistochemical counterpart (p53 mutant and score 3+ for HER2) can predict complete pathological response and the grade of response (P = .038 and P = .031, respectively). Therefore, p53 could be included in the initial panel of breast cancer biomarkers to help therapeutic decision-making in HER2+ cases.