Journal
CELL
Volume 185, Issue 2, Pages 299-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2021.12.023
Keywords
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Categories
Funding
- American Cancer Society Postdoctoral Fellowship [133099-PF-19-002-01-CCE]
- Stanford Immunology Training Grant [5 T32 AI07290-33]
- Bio-X Stanford Interdisciplinary Graduate Fellowship
- Stanford Graduate Fellowship
- NIH [RFA-CA-17-035]
- PCORI [1505-30497]
- BCRF [BCRF 19-074]
- DOD [BC132057, R01 CA185138-01]
- Bill and Melinda Gates Foundation
- Stanford Cancer Institute
- [R01CA193694]
- [U2C CA233254]
- [1-DP5-OD019822]
- [1R01AG056287]
- [1R01AG057915]
- [1U24CA224309]
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This study used MIBI-TOF and antibody staining methods to analyze the changes in the tumor microenvironment (TME) between DCIS and IBC. Four coordinated transitions between TME states were identified. The study also found that myoepithelial disruption was more advanced in DCIS patients who did not develop IBC, suggesting a potential protective effect against recurrence.
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.
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