Luz Paulo, Lopes-Brás Raquel, de Pinho Inês Soares, Patel Vanessa, Esperança-Martins Miguel, Gonçalves Lisa, Gonçalves Joana, Freitas Rita, Simão Diana, Galnares Maria Roldán, Criado Silvia Artacho, Nobre Amanda, Medina Elias A Gracia, Vega Isabel M Saffie, de Sousa Rita Teixeira, Costa Luís, Gregório João, Costa João G, Fernandes Ana S
CBIOS - Universidade Lusófona's Research Center for Biosciences & Health Technologies, Lisbon, Portugal.
Departament of Biomedical Sciences, Universidad de Alcalá, Madrid, Spain.
Clin Transl Oncol. 2025 May 10. doi: 10.1007/s12094-025-03937-7.
Neoadjuvant systemic therapy with dual HER2-blockade, trastuzumab and pertuzumab, combined with chemotherapy has become a standard approach in patients with HER2-positive (HER2+) breast cancer (BC). However, the variability in treatment outcomes, such as pathological complete response (pCR) or relapse rates, underscores the need to identify predictive factors to optimize therapeutic strategies. This study aims to explore the relationship between clinicopathological factors and both pCR and disease-free survival (DFS) in an international cohort of patients with HER2+ BC, contributing to defining personalized treatment strategies.
An international, multicenter, retrospective cohort study was conducted, including 517 patients with HER2+ BC who received neoadjuvant therapy comprising trastuzumab, pertuzumab, and chemotherapy. Data were collected between January 2016 and December 2023. The relationship between clinicopathological factors and treatment outcomes was analyzed using univariate tests, logistic regression for pCR, and Cox proportional hazards regression for DFS. Kaplan-Meier survival curves with log-rank tests and hazard ratios were used to compare DFS across subgroups.
Multivariable analysis revealed that hormonal receptor (HR) expression and nodal status significantly predicted the achievement of pCR in this cohort. Factors such as age, HR status, tumor grade, Ki-67 index, nodal status, and pathological response were associated with relapse risk.
Our real-world data demonstrates that a comprehensive approach considering pCR, age, HR status, and nodal involvement is essential for personalized treatment strategies. These factors should be taken into account when deciding whether to escalate or de-escalate treatment, contributing to improved HER2+ BC patient outcomes.
采用曲妥珠单抗和帕妥珠单抗双重HER2阻断联合化疗的新辅助全身治疗已成为HER2阳性（HER2+）乳腺癌（BC）患者的标准治疗方法。然而，治疗结果的变异性，如病理完全缓解（pCR）或复发率，凸显了识别预测因素以优化治疗策略的必要性。本研究旨在探讨国际队列中HER2+ BC患者的临床病理因素与pCR和无病生存期（DFS）之间的关系，为制定个性化治疗策略提供依据。
进行了一项国际多中心回顾性队列研究，纳入517例接受包含曲妥珠单抗、帕妥珠单抗和化疗的新辅助治疗的HER2+ BC患者。数据收集时间为2016年1月至2023年12月。采用单因素检验、pCR的逻辑回归分析以及DFS的Cox比例风险回归分析来分析临床病理因素与治疗结果之间的关系。使用Kaplan-Meier生存曲线及对数秩检验和风险比来比较各亚组的DFS。
多变量分析显示，激素受体（HR）表达和淋巴结状态显著预测了该队列中pCR的实现。年龄、HR状态、肿瘤分级、Ki-67指数、淋巴结状态和病理反应等因素与复发风险相关。
我们的真实世界数据表明，综合考虑pCR、年龄、HR状态和淋巴结受累情况的方法对于个性化治疗策略至关重要。在决定是否加强或减弱治疗时应考虑这些因素，有助于改善HER2+ BC患者的治疗结果。
