Comparative survival analysis of multiparametric tests—when molecular tests disagree—A TEAM Pathology study

npj Breast Cancer, vol. 7, pp. 90

Abstract

Abstract Multiparametric assays for risk stratification are widely used in the management of both node negative and node positive hormone receptor positive invasive breast cancer. Recent data from multiple sources suggests that different tests may provide different risk estimates at the individual patient level. The TEAM pathology study consists of 3284 postmenopausal ER+ve breast cancers treated with endocrine therapy Using genes comprising the following multi-parametric tests OncotypeDx ® , Prosigna™ and MammaPrint ® signatures were trained to recapitulate true assay results. Patients were then classified into risk groups and survival assessed. Whilst likelihood χ 2 ratios suggested limited value for combining tests, Kaplan–Meier and LogRank tests within risk groups suggested combinations of tests provided statistically significant stratification of potential clinical value. Paradoxically whilst Prosigna-trained results stratified Oncotype-trained subgroups across low and intermediate risk categories, only intermediate risk Prosigna-trained cases were further stratified by Oncotype-trained results. Both Oncotype-trained and Prosigna-trained results further stratified MammaPrint-trained low risk cases, and MammaPrint-trained results also stratified Oncotype-trained low and intermediate risk groups but not Prosigna-trained results. Comparisons between existing multiparametric tests are challenging, and evidence on discordance between tests in risk stratification presents further dilemmas. Detailed analysis of the TEAM pathology study suggests a complex inter-relationship between test results in the same patient cohorts which requires careful evaluation regarding test utility. Further prognostic improvement appears both desirable and achievable.

Authors 17

1. John M.S. Bartlett corresponding

   Ontario Institute for Cancer Research · University of Toronto · Edinburgh Cancer Research

   Affiliation as printed

   Diagnostic Development, Ontario Institute for Cancer Research, Toronto, ON, Canada. jbartlett@oicr.on.ca

   Edinburgh Cancer Research Centre, Edinburgh, UK. jbartlett@oicr.on.ca

   Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. jbartlett@oicr.on.ca

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

2. Jane Bayani

   Ontario Institute for Cancer Research

   Affiliation as printed

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

3. Elizabeth N. Kornaga

   Ontario Institute for Cancer Research

   Affiliation as printed

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

   Translational Laboratories, Tom Baker Cancer Centre, Calgary, AB, Canada

4. Keying Xu

   Ontario Institute for Cancer Research

   Affiliation as printed

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

5. Gregory R. Pond

   McMaster University

   Affiliation as printed

   Department of Oncology, McMaster University, Kingston, ON, Canada

6. Tammy Piper

   Edinburgh Cancer Research

   Affiliation as printed

   Edinburgh Cancer Research Centre, Edinburgh, UK

7. Elizabeth Mallon

   University of Glasgow

   Affiliation as printed

   Department of Pathology, Glasgow, UK

8. Cindy Q. Yao

   Ontario Institute for Cancer Research

   Affiliation as printed

   Informatics & Computational Biology, Ontario Institute for Cancer Research, Toronto, ON, Canada

9. Paul Christopher Boutros

   Ontario Institute for Cancer Research · University of California, Los Angeles · University of Toronto · UCLA Jonsson Comprehensive Cancer Center

   Affiliation as printed

   Department of Medical Biophysics, University of Toronto, Toronto, Canada

   Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada

   Informatics & Computational Biology, Ontario Institute for Cancer Research, Toronto, ON, Canada

   Jonsson Comprehensive Cancer Center, University of California, Los Angeles, USA

10. Annette Hasenburg

    Johannes Gutenberg University Mainz · University Medical Center of the Johannes Gutenberg University Mainz

    Affiliation as printed

    Dept of Gynecology and Obstetrics, University Center Mainz, Mainz, Germany

11. Janet Dunn

    University of Warwick

    Affiliation as printed

    University of Warwick, Coventry, UK

12. Christos J. Markopoulos

    National and Kapodistrian University of Athens

    Affiliation as printed

    National and Kapodistrian University of Athens, Medical School, Athens, Greece

13. Luc Yves Dirix

    GZA Ziekenhuizen Campus Sint-Augustinus

    Affiliation as printed

    St. Augustinus Hospital, Antwerp, Belgium

14. Caroline Seynaeve

    Erasmus MC Cancer Institute

    Affiliation as printed

    Erasmus MC Cancer Institute, Rotterdam, the Netherlands

15. Cornelis J.�H. van de Velde Aachen

    Leiden University Medical Center

    Affiliation as printed

    Leiden University Medical Center, Leiden, the Netherlands

16. Robert C. Stein

    National Institute for Health and Care Research · UCL Biomedical Research Centre · University College London

    Affiliation as printed

    National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, UK

17. 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, UK