Does RSClin provide additional information over classic clinico-pathologic scores (PREDICT 2.1, INFLUENCE 2.0, CTS5)?

The Breast, vol. 83, pp. 104528

Abstract

PURPOSE: Few studies have compared the performance of gene-expression profiling tests (e.g. Oncotype-Dx) to clinico-pathologic risk calculators (e.g. PREDICT 2.1, INFLUENCE 2.0, and CTS5) or tools that combine both (e.g. RSClin) in patients with early breast cancer (EBC). A large trial dataset was used to evaluate the prognostic performance of different tests based on patient outcomes. METHODS: The TEAM pathology cohort accrued samples from 4736 postmenopausal hormone positive women with EBC, treated with either exemestane or tamoxifen followed by exemestane. Oncotype-Dx-trained risk scores were previously generated by gene-expression profiling. Patient data was used to calculate various recurrence scores. Analysis was restricted to the N0/N1 population and prognostic ability of selected risk tools was assessed using Cox regression analysis and Harrell's C-statistic. RESULTS: Results were available for 2065 patients. There was low correlation between PREDICT 2.1 (r = -0.12), INFLUENCE 2.0 (r = 0.20), CTS5 (r = 0.16) with Oncotype-Dx-trained results. In N0 patients, RSClin had improved prognostic ability (C-statistic = 0.66) on DMFS compared to PREDICT 2.1 (0.60), INFLUENCE 2.0 (0.57), CTS-5 (0.62), and Oncotype-Dx (0.63). CONCLUSION: Combining molecular and clinico-pathologic factors enhances prognostic information. However, the impact of this on actual patient management requires further prospective validation. The trial is registered with clinicaltrials.gov NCT00279448 and NCT00032136; with Netherlands Trial Register, number NTR 267; and the Ethics Commission Trial, number 27/2001.

Authors 16

1. Ana-Alicia Beltran-Bless

   University of Ottawa

   Affiliation as printed

   Division of Medical Oncology, Department of Medicine, The University of Ottawa, Ottawa, Canada

2. Gregory R. Pond

   McMaster University

   Affiliation as printed

   Department of Oncology, McMaster University, Hamilton, Canada

3. Jane Bayani

   Ontario Institute for Cancer Research · University of Toronto

   Affiliation as printed

   Diagnostic Development, Ontario Institute for Cancer Research, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

4. Sarah L. Barker

   Ontario Institute for Cancer Research

   Affiliation as printed

   Diagnostic Development, Ontario Institute for Cancer Research, Toronto, Canada

5. Melanie Spears

   Ontario Institute for Cancer Research · University of Toronto

   Affiliation as printed

   Diagnostic Development, Ontario Institute for Cancer Research, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

6. Elizabeth Mallon

   University of Glasgow

   Affiliation as printed

   Department of Pathology, Glasgow, United Kingdom

7. Karen J. Taylor

   Edinburgh Cancer Research · University of Edinburgh

   Affiliation as printed

   Edinburgh Cancer Research, CRUK Scotland Centre, University of Edinburgh, Edinburgh, United Kingdom

8. Annette Hasenburg

   University Medical Center of the Johannes Gutenberg University Mainz

   Affiliation as printed

   Department of Gynecology and Obstetrics, University Center Mainz, Germany

9. Luc Yves Dirix

   GZA Ziekenhuizen Campus Sint-Augustinus

   Affiliation as printed

   St. Augustinus Hospital, Antwerp, Belgium

10. Elma Meershoek‐Klein Kranenbarg Aachen Department of Surgery, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands

11. Cornelis J.�H. van de Velde Aachen Department of Surgery, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands

12. Daniel William Rea

    Cancer Research UK Clinical Trials Unit · University of Birmingham

    Affiliation as printed

    Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom

13. Lisa Vandermeer

    Ottawa Hospital Research Institute

    Affiliation as printed

    Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, Canada

14. John Frederick Hilton

    University of Ottawa · Ottawa Hospital Research Institute

    Affiliation as printed

    Division of Medical Oncology, Department of Medicine, The University of Ottawa, Ottawa, Canada; Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, Canada

15. John M.S. Bartlett

    Edinburgh Cancer Research · University of Edinburgh

    Affiliation as printed

    Edinburgh Cancer Research, CRUK Scotland Centre, University of Edinburgh, Edinburgh, United Kingdom

16. Mark J. Clemons corresponding

    University of Ottawa · Ottawa Hospital Research Institute

    Affiliation as printed

    Division of Medical Oncology, Department of Medicine, The University of Ottawa, Ottawa, Canada; Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, Canada. Electronic address: mclemons@toh.ca