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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Risom, T; Glass, DR; Averbukh, I; Liu, CC; Baranski, A; Kagel, A; McCaffrey, EF; Greenwald, NF; Rivero-Gutiérrez, B; Strand, SH; Varma, S; Kong, A; Keren, L; Srivastava, S; Zhu, C; Khair, Z; Veis, DJ; Deschryver, K; Vennam, S; Maley, C; Hwang, ES; Marks, JR; Bendall, SC; Colditz, GA; West, RB; Angelo, M

Published Date

  • January 20, 2022

Published In

Volume / Issue

  • 185 / 2

Start / End Page

  • 299 - 310.e18

PubMed ID

  • 35063072

Pubmed Central ID

  • PMC8792442

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2021.12.023

Language

  • eng

Conference Location

  • United States