Spatial proteomic characterization of HER2-positive breast tumors through neoadjuvant therapy predicts response.

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.
AuthorsKatherine 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
JournalNature cancer (Nat Cancer) Vol. 2 Issue 4 Pg. 400-413 (04 2021) ISSN: 2662-1347 [Electronic] England
PMID34966897 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Receptor, ErbB-2
  • Trastuzumab
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Breast Neoplasms (drug therapy)
  • Female
  • Humans
  • Neoadjuvant Therapy
  • Proteomics
  • Receptor, ErbB-2 (genetics)
  • Trastuzumab

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!

Choose Username:
Verify Password:
Enter Code Shown: