双靶向药物治疗是HER2阳性乳腺癌的标准治疗方法。不过，预测术前曲妥珠单抗＋帕妥珠单抗新辅助治疗效果的生物标志物尚不明确。2022年5月19日，瑞士《免疫学前沿》在线发表复旦大学附属肿瘤医院丁佳涵、陈盛、余科达等学者的研究报告，开发了一个评估双靶向新辅助治疗对HER2基因扩增乳腺癌效果的预测模型。
该回顾研究对2020年1月1日～2021年6月30日复旦大学附属肿瘤医院连续159例HER2基因扩增局部晚期乳腺癌术前曲妥珠单抗＋帕妥珠单抗双靶向新辅助治疗联合化疗患者临床病理因素与病理完全缓解的相关性进行回顾分析。患者被随机分为训练集（110例）和测试集（49例），并通过外部独立队列（65例）进行验证。同时，采用多因素逻辑回归分析，确定病理完全缓解相关因素并构建预测列线图模型。采用受试者工作特征曲线、决策曲线分析和校准曲线的曲线下面积，对该模型的性能进行评估。
结果，对其他影响因素进行校正后，双靶向新辅助治疗后病理完全缓解的独立预测指标包括：
HER2/CEP17比值（P=0.001）
CD8水平（P=0.005）
组织学分级（P=0.007）
三项指标综合预测效能显著高于单项指标单独预测效能。训练集、测试集、外部验证集的曲线下面积分别达0.819、0.773、0.744。
因此，该研究结果表明，对于HER2阳性局部晚期乳腺癌术前双靶向新辅助治疗患者，HER2与CEP17比值、CD8水平、组织学分级与病理完全缓解显著相关，采用这三种标志物的组合模型对病理完全缓解的预测价值显著高于单独的HER2与CEP17比值、CD8水平以及组织学分级，免疫学效应可能部分影响新辅助治疗效果的预测。
Front Immunol. 2022 May 19;13:877825.
Predicting Pathological Complete Response in Neoadjuvant Dual Blockade With Trastuzumab and Pertuzumab in HER2 Gene Amplified Breast Cancer.
Yi Xiao, Jiahan Ding, Dachang Ma, Sheng Chen, Xun Li, Keda Yu.
The First Hospital of Lanzhou University, Lanzhou, China; Fudan University Shanghai Cancer Center, Shanghai, China.
BACKGROUND: Dual-targeted therapy is the standard treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and effective biomarkers to predict the response to neoadjuvant trastuzumab and pertuzumab treatment need further investigation. Here, we developed a predictive model to evaluate the dual-targeted neoadjuvant treatment efficacy in HER2 gene-amplified breast cancer.
METHOD: This retrospective study included 159 HER2-amplified patients with locally advanced breast cancer who received neoadjuvant trastuzumab, pertuzumab, and chemotherapy. The correlation between clinicopathological factors and pathological complete response (pCR, in the breast and axilla) was evaluated. Patients were randomly assigned into the training set (n=110) and the testing set (n=49). We used an independent cohort (n=65) for external validation. We constructed our predictive nomogram model with the results of risk variables associated with pCR identified in the multivariate logistic analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, decision curve analysis, and calibration curves were employed to assess the nomogram's performance.
RESULTS: We revealed that the HER2/CEP17 ratio (p=0.001), CD8 levels (p=0.005), and histological grade (p=0.007) were independent indicators for pCR in dual-targeted neoadjuvant treatment after multivariate adjustment. The combined prediction efficacy of the three indicators was significantly higher than that of each single indicator alone. The AUCs were 0.819, 0.773, and 0.744 in the training, testing, and external validation sets, respectively.
CONCLUSIONS: The HER2/CEP17 ratio, CD8 levels, and histological grade were significantly correlated with pCR in dual-targeted neoadjuvant treatment. The combined model using these three markers provided a better predictive value for pCR than the HER2/CEP17 ratio, CD8 levels, and the histological grade alone, which showed that an immunological effect partially mediates the predictive impact of neoadjuvant treatment.
KEYWORDS: trastuzumab, pertuzumab, predictive model, neoadjuvant treatment, HER2-amplified breast cancer
DOI: 10.3389/fimmu.2022.877825
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