Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma

Tyler Risom, David R. Glass, Inna Averbukh, Candace C. Liu, Alex Baranski, Adam Kagel, Erin F. McCaffrey, Noah F. Greenwald, Belén Rivero-Gutiérrez, Siri H. Strand, Sushama Varma, Alex Kong, Leeat Keren, Sucheta Srivastava, Chunfang Zhu, Zumana Khair, Deborah J. Veis, Katherine Deschryver, Sujay Vennam, Carlo MaleyE. Shelley Hwang, Jeffrey R. Marks, Sean C. Bendall, Graham A. Colditz, Robert B. West, Michael Angelo

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor to invasive breast cancer (IBC). To understand the changes in the tumor microenvironment (TME) accompanying transition to IBC, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) and a 37-plex antibody staining panel to interrogate 79 clinically annotated surgical resections using machine learning tools for cell segmentation, pixel-based clustering, and object morphometrics. Comparison of normal breast with patient-matched DCIS and IBC revealed coordinated transitions between four TME states that were delineated based on the location and function of myoepithelium, fibroblasts, and immune cells. Surprisingly, myoepithelial disruption was more advanced in DCIS patients that did not develop IBC, suggesting this process could be protective against recurrence. Taken together, this HTAN Breast PreCancer Atlas study offers insight into drivers of IBC relapse and emphasizes the importance of the TME in regulating these processes.

Original languageEnglish (US)
Pages (from-to)299-310.e18
JournalCell
Volume185
Issue number2
DOIs
StatePublished - Jan 20 2022
Externally publishedYes

Keywords

  • DCIS
  • MIBI
  • breast cancer
  • myoepithelium
  • spatial proteomics
  • systems biology
  • tumor microenvironment
  • tumor progression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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