Influence of HER2 Changes on Survival Outcomes After Neoadjuvant Chemotherapy in Peruvian Patients With Triple-Negative Breast Cancer

Abstract

Background: Lack of human epidermal growth factor receptor 2 (HER2) expression limits targeted treatments for triple-negative breast cancer (TNBC). HER2 status changes after neoadjuvant chemotherapy (NAC) have been reported, but their impact on survival in Peruvian TNBC patients remains unexplored. Here, we aimed to assess HER2 status before and after NAC and its association with clinical characteristics, treatment response, and survival outcomes. Methods: Our analysis included clinicopathological data from 159 TNBC patients diagnosed between 2015 and 2019 at the Instituto Nacional de Enfermedades Neoplásicas (Lima, Peru) who received NAC. Logistic regression was used to assess the association between HER2 status at diagnosis and pathological complete response (pCR). Cohen’s Kappa analysis evaluated the agreement between pre- and post-NAC HER2 status, while Kaplan–Meier analysis estimated the impact of HER2 changes on overall survival (OS) and disease-free survival (DFS). Results: Among TNBC patients, 40.3% were HER2-low at diagnosis and 14.9% achieved pCR. Pretherapeutic HER2 status was not associated with pCR (OR = 1.4, 95% CI = 0.55–3.61, and p = 0.5). HER2 status remained unchanged in 62.8% of HER2-zero and 75.9% of HER2-low patients post-NAC, showing moderate concordance (Cohen’s kappa = 0.3418, p < 0.001). No significant OS improvements were observed in patients with HER2 transitions: HER2-zero/HER2-low (HR = 0.52, 95% CI = 0.22–1.24, and p = 0.14), HER2-low/HER2-zero (HR = 0.9, 95% CI = 0.34–2.40, and p = 0.8), or HER2-low/HER2-low (HR = 0.71, 95% CI = 0.34–1.49, and p = 0.4) compared with HER2-zero/HER2-zero. Similar findings were reported for DFS. Conclusion: These findings suggest that HER2 status conversion may not be prognostic for patients with TNBC treated with neoadjuvant therapy. Copyright © 2025 Zaida Morante et al. The Breast Journal published by John Wiley & Sons Ltd.