TY - JOUR
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.
N1 - Funding Information:
This publication is part of the HTAN (Human Tumor Atlas Network) Consortium paper package. A list of HTAN members is available at humantumoratlas.org/htan-authors/ . R01 CA185138-01 (E.S.H.); U2C CA-17-035 Pre-Cancer Atlas (PCA) Research Centers (E.S.H., R.B.W., C.M., K.P., G.A.C., K.O.); UO1 CA214183 (J.R.M.); DOD BC132057 (E.S.H., C.M.); BCRF 19-074 (E.S.H.); BCRF 19-028 (G.A.C.); PRECISION CRUK Grand Challenge (E.S.H.); R01CA193694 (R.B.W., G.A.C.), BCRF PPI-18-006 (R.B.W.). AEI RYC2019- 026576-I , " LaCaixa" Foundation LCF/PR/PR17/51120011 (J.A.S.). S.H.S. was supported by the Lundbeck Foundation ( R288-2018-35 ) and the Danish Cancer Society ( R229-A13616 ). K.E.H. was supported by a CIHR Banting Postdoctoral Fellowship. TBCRC 038 was conducted by the TBCRC, which receives major funding support from The Breast Cancer Research Foundation and Susan G. Komen. Some results in this paper are based upon data generated by the TCGA Research Network. 34
Funding Information:
This publication is part of the HTAN (Human Tumor Atlas Network) Consortium paper package. A list of HTAN members is available at humantumoratlas.org/htan-authors/. R01 CA185138-01 (E.S.H.); U2C CA-17-035 Pre-Cancer Atlas (PCA) Research Centers (E.S.H. R.B.W. C.M. K.P. G.A.C. K.O.); UO1 CA214183 (J.R.M.); DOD BC132057 (E.S.H. C.M.); BCRF 19-074 (E.S.H.); BCRF 19-028 (G.A.C.); PRECISION CRUK Grand Challenge (E.S.H.); R01CA193694 (R.B.W. G.A.C.), BCRF PPI-18-006 (R.B.W.). AEI RYC2019- 026576-I, “LaCaixa” Foundation LCF/PR/PR17/51120011 (J.A.S.). S.H.S. was supported by the Lundbeck Foundation (R288-2018-35) and the Danish Cancer Society (R229-A13616). K.E.H. was supported by a CIHR Banting Postdoctoral Fellowship. TBCRC 038 was conducted by the TBCRC, which receives major funding support from The Breast Cancer Research Foundation and Susan G. Komen. Some results in this paper are based upon data generated by the TCGA Research Network.34, Conceptualization: E.S.H. R.B.W. C.M. G.A.C. J.R.M. C.C. and K.P. Investigation: S.H.S. B.R.G. K.E.H. J.A.S. T.R. S.Vennam, A.K. L.C. D.J.V. K.D. D.Y.D. D.Z. J.L. S.J. S.S. A.H. and R.B.W. Resources: L.A.S. T.H. B.H. F.C. K.G. M.K. S.W. A.D. T.K. P.M. J.N. J.L. J.Tseng, A.M.S. A.T. G.G. C.Z. M.M. J.W. S.X.Z. and S.Varma. Data curation: L.K. and J.Tappenden. Writing – original draft: S.H.S. B.R.G. K.E.H. J.R.M. E.S.H. and R.B.W. Writing – review & editing: all co-authors. Funding acquisition: E.S.H. R.B.W. G.A.C. and C.M. Project administration: R.B. L.A. and C.S. Supervision: C.C. R.T. R.M.A. K.O. K.P. C.M. J.R.M. G.A.C. E.S.H. and R.B.W. C.C. serves on the Scientific Advisory Board and/or as consultant for GRAIL, Deepcell, Ravel, Viosera, NanoString, and Genentech and holds equity in GRAIL, Deepcell, and Ravel. K.P. serves on the Scientific Advisory Board of Acrivon Therapeutics, Vividion Therapeutics, and Scorpion Therapeutics, holds equity in Scorpion Therapeutics and Vividion Therapeutics, is a consultant to Aria Pharmaceuticals, and received honorarium from Astra-Zeneca. R.M.A. is an inventor on patent US20150287578A and board member and shareholder in IonPath Inc. T.R. and R.B.W. have consulted for IonPath Inc.
Publisher Copyright:
© 2022 The Author(s)
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
UR - http://www.scopus.com/inward/record.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
AN - SCOPUS:85143975745
SN - 1535-6108
VL - 40
SP - 1521-1536.e7
JO - Cancer Cell
JF - Cancer Cell
IS - 12
ER -