新辅助治疗
医学
乳腺癌
靶向治疗
肿瘤科
内科学
化疗
免疫组织化学
多路复用
癌症
生物信息学
生物
作者
Katherine McNamara,Jennifer L. Caswell-Jin,Rohan P. Joshi,Zhicheng Ma,Eran Kotler,Gregory R. Bean,Michelle Kriner,Zhenpeng Zhou,Margaret L. Hoang,Joseph M. Beechem,Jason J. Zoeller,Michael F. Press,Dennis J. Slamon,Sara A. Hurvitz,Christina Curtis
出处
期刊:Nature cancer
[Springer Nature]
日期:2021-04-08
卷期号:2 (4): 400-413
被引量:37
标识
DOI:10.1038/s43018-021-00190-z
摘要
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.
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