The addition of HER2-targeted agents to neoadjuvant chemotherapy has dramatically improved pathological complete response (pCR) rates in early-stage, HER2-positive breast cancer. Nonetheless, up to 50% of patients have residual disease after treatment, while others are likely overtreated. Here, we performed multiplex spatial proteomic characterization of 122 samples from 57 HER2-positive breast tumors from the neoadjuvant TRIO-US B07 clinical trial sampled pre-treatment, after 14–21 d of HER2-targeted therapy and at surgery. We demonstrated that proteomic changes after a single cycle of HER2-targeted therapy aids the identification of tumors that ultimately undergo pCR, outperforming pre-treatment measures or transcriptomic changes. We further developed and validated a classifier that robustly predicted pCR using a single marker, CD45, measured on treatment, and showed that CD45-positive cell counts measured via conventional immunohistochemistry perform comparably. These results demonstrate robust biomarkers that can be used to enable the stratification of sensitive tumors early during neoadjuvant HER2-targeted therapy, with implications for tailoring subsequent therapy.
在早期的HER2阳性乳腺癌患者中，将HER2靶向药物与新辅助化疗联合使用显著提高了病理完全应答（pCR）率。然而，仍有高达50%的患者治疗后残留疾病，其他患者可能接受过度治疗。我们通过多基因组定位质谱分析对TRIO-US B07临床试验中57例HER2阳性乳腺肿瘤的122份样本进行了多基因组定位质谱分析，分别在术前、入院后14-21天和手术后。我们证明单次赫拉巴特异性治疗后的蛋白变化有助于识别最终获得pCR的肿瘤，并且优于预处理方法或转录组变化。我们进一步开发并验证了一个基于CD45单一标记的分类器，该分类器能够可靠地预测pCR，并通过常规免疫组织化学方法测量CD45阳性细胞计数来验证其性能。这些结果表明，可以使用这些稳健的生物标志物在新辅助HER2靶向治疗早期对易感肿瘤进行分层，为后续治疗个性化治疗提供依据。
肿瘤(癌症)患者之家