Spatial proteomic characterization of HER2-positive breast tumors through neoadjuvant therapy predicts response.
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| Abstract |
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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| Authors | Katherine L McNamara, Jennifer L Caswell-Jin, Rohan Joshi, Zhicheng Ma, Eran Kotler, Gregory R Bean, Michelle Kriner, Zoey Zhou, Margaret Hoang, Joseph Beechem, Jason Zoeller, Michael F Press, Dennis J Slamon, Sara A Hurvitz, Christina Curtis |
| Journal | Nature cancer (Nat Cancer) Vol. 2 Issue 4 Pg. 400-413 (04 2021) ISSN: 2662-1347 [Electronic] England |
| PMID | 34966897 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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