Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts

Siri H. Strand; Belén Rivero-Gutiérrez; Kathleen E. Houlahan; Jose A. Seoane; Lorraine M. King; Tyler Risom; Lunden A. Simpson; Sujay Vennam; Aziz Khan; Luis Cisneros; Timothy Hardman; Bryan Harmon; Fergus Couch; Kristalyn Gallagher; Mark Kilgore; Shi Wei; Angela DeMichele; Tari King; Priscilla F. McAuliffe; Julie Nangia; Joanna Lee; Jennifer Tseng; Anna Maria Storniolo; Alastair M. Thompson; Gaorav P. Gupta; Robyn Burns; Deborah J. Veis; Katherine DeSchryver; Chunfang Zhu; Magdalena Matusiak; Jason Wang; Shirley X. Zhu; Jen Tappenden; Daisy Yi Ding; Dadong Zhang; Jingqin Luo; Shu Jiang; Sushama Varma; Lauren Anderson; Cody Straub; Sucheta Srivastava; Christina Curtis; Rob Tibshirani; Robert Michael Angelo; Allison Hall; Kouros Owzar; Kornelia Polyak; Carlo Maley; Jeffrey R. Marks; Graham A. Colditz; E. Shelley Hwang; Robert B. West

doi:10.1016/j.ccell.2022.10.021

Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts

Siri H. Strand, Belén Rivero-Gutiérrez, Kathleen E. Houlahan, Jose A. Seoane, Lorraine M. King, Tyler Risom, Lunden A. Simpson, Sujay Vennam, Aziz Khan, Luis Cisneros, Timothy Hardman, Bryan Harmon, Fergus Couch, Kristalyn Gallagher, Mark Kilgore, Shi Wei, Angela DeMichele, Tari King, Priscilla F. McAuliffe, Julie NangiaJoanna Lee, Jennifer Tseng, Anna Maria Storniolo, Alastair M. Thompson, Gaorav P. Gupta, Robyn Burns, Deborah J. Veis, Katherine DeSchryver, Chunfang Zhu, Magdalena Matusiak, Jason Wang, Shirley X. Zhu, Jen Tappenden, Daisy Yi Ding, Dadong Zhang, Jingqin Luo, Shu Jiang, Sushama Varma, Lauren Anderson, Cody Straub, Sucheta Srivastava, Christina Curtis, Rob Tibshirani, Robert Michael Angelo, Allison Hall, Kouros Owzar, Kornelia Polyak, Carlo Maley, Jeffrey R. Marks, Graham A. Colditz, E. Shelley Hwang, Robert B. West

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Translational Breast Cancer Research Consortium 038 study and the Resource of Archival Breast Tissue cohorts. We identify 812 genes associated with ipsilateral recurrence within 5 years from treatment and develop a classifier that predicts DCIS or IBC recurrence in both cohorts. Pathways associated with recurrence include proliferation, immune response, and metabolism. Distinct stromal expression patterns and immune cell compositions are identified. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.

Original language	English (US)
Pages (from-to)	1521-1536.e7
Journal	Cancer cell
Volume	40
Issue number	12
DOIs	https://doi.org/10.1016/j.ccell.2022.10.021
State	Published - Dec 12 2022

Keywords

RNA gene expression profiling
breast
classifier
ductal carcinoma in situ
multiplex immunohistochemistry
precancer
prognosis
progression
tumor microenvironment
whole genome sequencing

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccell.2022.10.021

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Strand, S. H., Rivero-Gutiérrez, B., Houlahan, K. E., Seoane, J. A., King, L. M., Risom, T., Simpson, L. A., Vennam, S., Khan, A., Cisneros, L., Hardman, T., Harmon, B., Couch, F., Gallagher, K., Kilgore, M., Wei, S., DeMichele, A., King, T., McAuliffe, P. F., ... West, R. B. (2022). Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts. Cancer cell, 40(12), 1521-1536.e7. https://doi.org/10.1016/j.ccell.2022.10.021

Strand, SH, Rivero-Gutiérrez, B, Houlahan, KE, Seoane, JA, King, LM, Risom, T, Simpson, LA, Vennam, S, Khan, A, Cisneros, L, Hardman, T, Harmon, B, Couch, F, Gallagher, K, Kilgore, M, Wei, S, DeMichele, A, King, T, McAuliffe, PF, Nangia, J, Lee, J, Tseng, J, Storniolo, AM, Thompson, AM, Gupta, GP, Burns, R, Veis, DJ, DeSchryver, K, Zhu, C, Matusiak, M, Wang, J, Zhu, SX, Tappenden, J, Ding, DY, Zhang, D, Luo, J, Jiang, S, Varma, S, Anderson, L, Straub, C, Srivastava, S, Curtis, C, Tibshirani, R, Angelo, RM, Hall, A, Owzar, K, Polyak, K, Maley, C, Marks, JR, Colditz, GA, Hwang, ES & West, RB 2022, 'Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts', Cancer cell, vol. 40, no. 12, pp. 1521-1536.e7. https://doi.org/10.1016/j.ccell.2022.10.021

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title = "Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts",

abstract = "Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Translational Breast Cancer Research Consortium 038 study and the Resource of Archival Breast Tissue cohorts. We identify 812 genes associated with ipsilateral recurrence within 5 years from treatment and develop a classifier that predicts DCIS or IBC recurrence in both cohorts. Pathways associated with recurrence include proliferation, immune response, and metabolism. Distinct stromal expression patterns and immune cell compositions are identified. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.",

keywords = "RNA gene expression profiling, breast, classifier, ductal carcinoma in situ, multiplex immunohistochemistry, precancer, prognosis, progression, tumor microenvironment, whole genome sequencing",

author = "Strand, {Siri H.} and Bel{\'e}n Rivero-Guti{\'e}rrez and Houlahan, {Kathleen E.} and Seoane, {Jose A.} and King, {Lorraine M.} and Tyler Risom and Simpson, {Lunden A.} and Sujay Vennam and Aziz Khan and Luis Cisneros and Timothy Hardman and Bryan Harmon and Fergus Couch and Kristalyn Gallagher and Mark Kilgore and Shi Wei and Angela DeMichele and Tari King and McAuliffe, {Priscilla F.} and Julie Nangia and Joanna Lee and Jennifer Tseng and Storniolo, {Anna Maria} and Thompson, {Alastair M.} and Gupta, {Gaorav P.} and Robyn Burns and Veis, {Deborah J.} and Katherine DeSchryver and Chunfang Zhu and Magdalena Matusiak and Jason Wang and Zhu, {Shirley X.} and Jen Tappenden and Ding, {Daisy Yi} and Dadong Zhang and Jingqin Luo and Shu Jiang and Sushama Varma and Lauren Anderson and Cody Straub and Sucheta Srivastava and Christina Curtis and Rob Tibshirani and Angelo, {Robert Michael} and Allison Hall and Kouros Owzar and Kornelia Polyak and Carlo Maley and Marks, {Jeffrey R.} and Colditz, {Graham A.} and Hwang, {E. Shelley} and West, {Robert B.}",

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year = "2022",

month = dec,

day = "12",

doi = "10.1016/j.ccell.2022.10.021",

language = "English (US)",

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T1 - Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ

T2 - Analysis of TBCRC 038 and RAHBT cohorts

AU - Strand, Siri H.

AU - Rivero-Gutiérrez, Belén

AU - Houlahan, Kathleen E.

AU - Seoane, Jose A.

AU - King, Lorraine M.

AU - Risom, Tyler

AU - Simpson, Lunden A.

AU - Vennam, Sujay

AU - Khan, Aziz

AU - Cisneros, Luis

AU - Hardman, Timothy

AU - Harmon, Bryan

AU - Couch, Fergus

AU - Gallagher, Kristalyn

AU - Kilgore, Mark

AU - Wei, Shi

AU - DeMichele, Angela

AU - King, Tari

AU - McAuliffe, Priscilla F.

AU - Nangia, Julie

AU - Lee, Joanna

AU - Tseng, Jennifer

AU - Storniolo, Anna Maria

AU - Thompson, Alastair M.

AU - Gupta, Gaorav P.

AU - Burns, Robyn

AU - Veis, Deborah J.

AU - DeSchryver, Katherine

AU - Zhu, Chunfang

AU - Matusiak, Magdalena

AU - Wang, Jason

AU - Zhu, Shirley X.

AU - Tappenden, Jen

AU - Ding, Daisy Yi

AU - Zhang, Dadong

AU - Luo, Jingqin

AU - Jiang, Shu

AU - Varma, Sushama

AU - Anderson, Lauren

AU - Straub, Cody

AU - Srivastava, Sucheta

AU - Curtis, Christina

AU - Tibshirani, Rob

AU - Angelo, Robert Michael

AU - Hall, Allison

AU - Owzar, Kouros

AU - Polyak, Kornelia

AU - Maley, Carlo

AU - Marks, Jeffrey R.

AU - Colditz, Graham A.

AU - Hwang, E. Shelley

AU - West, Robert B.

PY - 2022/12/12

Y1 - 2022/12/12

N2 - Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Translational Breast Cancer Research Consortium 038 study and the Resource of Archival Breast Tissue cohorts. We identify 812 genes associated with ipsilateral recurrence within 5 years from treatment and develop a classifier that predicts DCIS or IBC recurrence in both cohorts. Pathways associated with recurrence include proliferation, immune response, and metabolism. Distinct stromal expression patterns and immune cell compositions are identified. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.

AB - Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Translational Breast Cancer Research Consortium 038 study and the Resource of Archival Breast Tissue cohorts. We identify 812 genes associated with ipsilateral recurrence within 5 years from treatment and develop a classifier that predicts DCIS or IBC recurrence in both cohorts. Pathways associated with recurrence include proliferation, immune response, and metabolism. Distinct stromal expression patterns and immune cell compositions are identified. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.

KW - RNA gene expression profiling

KW - breast

KW - classifier

KW - ductal carcinoma in situ

KW - multiplex immunohistochemistry

KW - precancer

KW - prognosis

KW - progression

KW - tumor microenvironment

KW - whole genome sequencing

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UR - http://www.scopus.com/inward/citedby.url?scp=85143975745&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2022.10.021

DO - 10.1016/j.ccell.2022.10.021

M3 - Article

C2 - 36400020

SN - 1535-6108

VL - 40

SP - 1521-1536.e7

JO - Cancer cell

JF - Cancer cell

IS - 12

ER -

Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

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Researchers develop gene classifier to predict DCIS risk of cancer progression

Study Results from Stanford University in the Area of Breast Cancer Reported (Molecular Classification and Biomarkers of Clinical Outcome In Breast Ductal Carcinoma In Situ: Analysis of Tbcrc 038 and Rahbt Cohorts)

New gene classifier can predict the risk of cancer cells recurring or progressing

Cite this

Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Press/Media

Researchers develop gene classifier to predict DCIS risk of cancer progression

Study Results from Stanford University in the Area of Breast Cancer Reported (Molecular Classification and Biomarkers of Clinical Outcome In Breast Ductal Carcinoma In Situ: Analysis of Tbcrc 038 and Rahbt Cohorts)

New gene classifier can predict the risk of cancer cells recurring or progressing

Cite this