A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor-positive breast cancer Public Deposited

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  • Perou, Charles
    • ORCID: https://orcid.org/0000-0001-9827-2247
    • Affiliation: School of Medicine, Department of Genetics, Department of Pathology and Laboratory Medicine, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Davies, Sherri R.
    • Other Affiliation: Department of Medicine, Division of Oncology, Washington University School of Medicine, St Louis, Missouri
  • Nielsen, Torsten O.
    • Other Affiliation: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada
  • Bernard, Philip S.
    • Other Affiliation: Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah
  • Cheang, Maggie C.U.
    • Affiliation: School of Medicine, Department of Genetics, Department of Pathology and Laboratory Medicine, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
    • Other Affiliation: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada
  • Ellis, Matthew J.
    • Other Affiliation: Department of Medicine, Division of Oncology, Washington University School of Medicine, St Louis, Missouri; Siteman Comprehensive Cancer Center, Washington University School of Medicine and Barnes-Jewish Hospital, St Louis, Missouri
  • Voduc, David
    • Other Affiliation: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada
  • Leung, Samuel
    • Other Affiliation: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada
  • Parker, Joel
    • Affiliation: School of Medicine, Department of Genetics, Department of Pathology and Laboratory Medicine, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Vickery, Tammi
    • Other Affiliation: Department of Genetics, The Genome Center, Washington University School of Medicine, St Louis, Missouri
  • Stijleman, Inge J.
    • Other Affiliation: Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah
  • Reed, Jerry
    • Other Affiliation: Department of Genetics, The Genome Center, Washington University School of Medicine, St Louis, Missouri
  • Ebbert, Mark
    • Other Affiliation: Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah
  • Snider, Jacqueline
    • Other Affiliation: Department of Medicine, Division of Oncology, Washington University School of Medicine, St Louis, Missouri
  • Mardis, Elaine R.
    • Other Affiliation: Department of Genetics, The Genome Center, Washington University School of Medicine, St Louis, Missouri; Siteman Comprehensive Cancer Center, Washington University School of Medicine and Barnes-Jewish Hospital, St Louis, Missouri
Abstract
  • Purpose: To compare clinical, immunohistochemical (IHC), and gene expression models of prognosis applicable to formalin-fixed, paraffin-embedded blocks in a large series of estrogen receptor (ER)–positive breast cancers from patients uniformly treated with adjuvant tamoxifen. Experimental Design: Quantitative real-time reverse transcription-PCR (qRT-PCR) assays for 50 genes identifying intrinsic breast cancer subtypes were completed on 786 specimens linked to clinical (median follow-up, 11.7 years) and IHC [ER, progesterone receptor (PR), HER2, and Ki67] data. Performance of predefined intrinsic subtype and risk-of-relapse scores was assessed using multivariable Cox models and Kaplan-Meier analysis. Harrell's C-index was used to compare fixed models trained in independent data sets, including proliferation signatures. Results: Despite clinical ER positivity, 10% of cases were assigned to nonluminal subtypes. qRT-PCR signatures for proliferation genes gave more prognostic information than clinical assays for hormone receptors or Ki67. In Cox models incorporating standard prognostic variables, hazard ratios for breast cancer disease-specific survival over the first 5 years of follow-up, relative to the most common luminal A subtype, are 1.99 [95% confidence interval (CI), 1.09-3.64] for luminal B, 3.65 (95% CI, 1.64-8.16) for HER2-enriched subtype, and 17.71 (95% CI, 1.71-183.33) for the basal-like subtype. For node-negative disease, PAM50 qRT-PCR–based risk assignment weighted for tumor size and proliferation identifies a group with >95% 10-year survival without chemotherapy. In node-positive disease, PAM50-based prognostic models were also superior. Conclusion: The PAM50 gene expression test for intrinsic biological subtype can be applied to large series of formalin-fixed, paraffin-embedded breast cancers, and gives more prognostic information than clinical factors and IHC using standard cut points.
Date of publication
Identifier
  • 2-s2.0-78049453780
  • doi:10.1158/1078-0432.CCR-10-1282
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Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Clinical Cancer Research
Journal volume
  • 16
Journal issue
  • 21
Page start
  • 5222
Page end
  • 5232
Language
  • English
Version
  • Postprint
ISSN
  • 1078-0432
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