1. Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma
- Author
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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 Maley, E. Shelley Hwang, Jeffrey R. Marks, Sean C. Bendall, Graham A. Colditz, Robert B. West, and Michael Angelo
- Subjects
Breast Neoplasms ,Cell Differentiation ,Epithelial Cells ,Fibroblasts ,Middle Aged ,Epithelium ,Article ,General Biochemistry, Genetics and Molecular Biology ,Extracellular Matrix ,Cohort Studies ,Carcinoma, Intraductal, Noninfiltrating ,Phenotype ,Disease Progression ,Tumor Microenvironment ,Humans ,Female ,Neoplasm Invasiveness ,sense organs ,Neoplasm Recurrence, Local ,Single-Cell Analysis ,Stromal Cells ,skin and connective tissue diseases - Abstract
SUMMARY 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., In brief A spatial imaging atlas of patient-matched ductal carcinoma in situ and invasive breast cancer depicts coordinated changes in the tumor microenviroment associated with invasive relapse, suggesting a potential protective role of myoepithelial disruption against invasive progression., Graphical Abstract
- Published
- 2022