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 journalArticlepeer-review

24 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 languageEnglish (US)
Pages (from-to)1521-1536.e7
JournalCancer cell
Volume40
Issue number12
DOIs
StatePublished - 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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