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 Maley; E. Shelley Hwang; Jeffrey R. Marks; Sean C. Bendall; Graham A. Colditz; Robert B. West; Michael Angelo

doi:10.1016/j.cell.2021.12.023

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 journal › Article › peer-review

157 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 language	English
Pages (from-to)	299-310.e18
Journal	Cell
Volume	185
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2021.12.023
State	Published - Jan 20 2022

Keywords

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

Access to Document

10.1016/j.cell.2021.12.023

Cite this

Risom, T., Glass, D. R., Averbukh, I., Liu, C. C., Baranski, A., Kagel, A., McCaffrey, E. F., Greenwald, N. F., Rivero-Gutiérrez, B., Strand, S. H., Varma, S., Kong, A., Keren, L., Srivastava, S., Zhu, C., Khair, Z., Veis, D. J., Deschryver, K., Vennam, S., ... Angelo, M. (2022). Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma. Cell, 185(2), 299-310.e18. https://doi.org/10.1016/j.cell.2021.12.023

@article{923cb77e4b1047e583175b44782a66ff,

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

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.",

keywords = "DCIS, MIBI, breast cancer, myoepithelium, spatial proteomics, systems biology, tumor microenvironment, tumor progression",

author = "Tyler Risom and Glass, {David R.} and Inna Averbukh and Liu, {Candace C.} and Alex Baranski and Adam Kagel and McCaffrey, {Erin F.} and Greenwald, {Noah F.} and Bel{\'e}n Rivero-Guti{\'e}rrez and Strand, {Siri H.} and Sushama Varma and Alex Kong and Leeat Keren and Sucheta Srivastava and Chunfang Zhu and Zumana Khair and Veis, {Deborah J.} and Katherine Deschryver and Sujay Vennam and Carlo Maley and Hwang, {E. Shelley} and Marks, {Jeffrey R.} and Bendall, {Sean C.} and Colditz, {Graham A.} and West, {Robert B.} and Michael Angelo",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = jan,

day = "20",

doi = "10.1016/j.cell.2021.12.023",

language = "English",

volume = "185",

pages = "299--310.e18",

journal = "Cell",

issn = "0092-8674",

number = "2",

}

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 2022, 'Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma', Cell, vol. 185, no. 2, pp. 299-310.e18. https://doi.org/10.1016/j.cell.2021.12.023

TY - JOUR

T1 - Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma

AU - Risom, Tyler

AU - Glass, David R.

AU - Averbukh, Inna

AU - Liu, Candace C.

AU - Baranski, Alex

AU - Kagel, Adam

AU - McCaffrey, Erin F.

AU - Greenwald, Noah F.

AU - Rivero-Gutiérrez, Belén

AU - Strand, Siri H.

AU - Varma, Sushama

AU - Kong, Alex

AU - Keren, Leeat

AU - Srivastava, Sucheta

AU - Zhu, Chunfang

AU - Khair, Zumana

AU - Veis, Deborah J.

AU - Deschryver, Katherine

AU - Vennam, Sujay

AU - Maley, Carlo

AU - Hwang, E. Shelley

AU - Marks, Jeffrey R.

AU - Bendall, Sean C.

AU - Colditz, Graham A.

AU - West, Robert B.

AU - Angelo, Michael

PY - 2022/1/20

Y1 - 2022/1/20

N2 - 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.

AB - 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.

KW - DCIS

KW - MIBI

KW - breast cancer

KW - myoepithelium

KW - spatial proteomics

KW - systems biology

KW - tumor microenvironment

KW - tumor progression

UR - http://www.scopus.com/inward/record.url?scp=85123260803&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2021.12.023

DO - 10.1016/j.cell.2021.12.023

M3 - Article

C2 - 35063072

AN - SCOPUS:85123260803

SN - 0092-8674

VL - 185

SP - 299-310.e18

JO - Cell

JF - Cell

IS - 2

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this