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Incorporating progesterone receptor expression into the PREDICT breast prognostic model

Grootes I 1 , Keeman R 2 , Blows FM 3 , Milne RL 4 , Giles GG 4 , Swerdlow AJ 5 Show all authors , Fasching PA 6 , Abubakar M 7 , Andrulis IL 8 , Anton-Culver H 9 , Beckmann MW 10 , Blomqvist C 11 , Bojesen SE 12 , Bolla MK 13 , Bonanni B 14 , Briceno I 15 , Burwinkel B 16 , Camp NJ 17 , Castelao JE 18 , Choi JY 19 , Clarke CL 20 , Couch FJ 21 , Cox A 22 , Cross SS 23 , Czene K 24 , Devilee P 25 , Dörk T 26 , Dunning AM 3 , Dwek M 27 , Easton DF 28 , Eccles DM 29 , Eriksson M 24 , Ernst K 30 , Evans DG 31 , Figueroa JD 32 , Fink V 30 , Floris G 33 , Fox S 34 , Gabrielson M 24 , Gago-Dominguez M 35 , García-Sáenz JA 36 , González-Neira A 37 , Haeberle L 10 , Haiman CA 38 , Hall P 39 , Hamann U 40 , Harkness EF 41 , Hartman M 42 , Hein A 10 , Hooning MJ 43 , Hou MF 44 , Howell SJ 45 , ABCTB Investigators 46 , kConFab Investigators 47 , Ito H 48 , Jakubowska A 49 , Janni W 30 , John EM 50 , Jung A 51 , Kang D 52 , Kristensen VN 53 , Kwong A 54 , Lambrechts D 55 , Li J 56 , Lubiński J 57 , Manoochehri M 40 , Margolin S 58 , Matsuo K 59 , Taib NAM 60 , Mulligan AM 61 , Nevanlinna H 62 , Newman WG 31 , Offit K 63 , Osorio A 64 , Park SK 65 , Park-Simon TW 26 , Patel AV 66 , Presneau N 27 , Pylkäs K 67 , Rack B 30 , Radice P 68 , Rennert G 69 , Romero A 70 , Saloustros E 71 , Sawyer EJ 72 , Schneeweiss A 73 , Schochter F 30 , Schoemaker MJ 74 , Shen CY 75 , Shibli R 69 , Sinn P 76 , Tapper WJ 29 , Tawfiq E 77 , Teo SH 78 , Teras LR 66 , Torres D 79 , Vachon CM 80 , van Deurzen CHM 81 , Wendt C 82 , Williams JA 17 , Winqvist R 67 , Elwood M 77 , Schmidt MK 83 , García-Closas M 7 , Pharoah PDP 28

Affiliations 

  • 1 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, CB1 8RN, UK. Electronic address: [email protected]
  • 2 The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam, 1066 CX, the Netherlands
  • 3 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, CB1 8RN, UK
  • 4 Cancer Council Victoria, Cancer Epidemiology Division, Melbourne, Victoria, 3004, Australia; The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, Victoria, 3010, Australia; Monash University, Precision Medicine, School of Clinical Sciences at Monash Health, Clayton, Victoria, 3168, Australia
  • 5 The Institute of Cancer Research, Division of Genetics and Epidemiology, London, SM2 5NG, UK; The Institute of Cancer Research, Division of Breast Cancer Research, London, SW7 3RP, UK
  • 6 University of California at Los Angeles, David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, Los Angeles, CA, 90095, USA; Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Department of Gynecology and Obstetrics, Erlangen, 91054, Germany
  • 7 National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, Bethesda, MD, 20850, USA
  • 8 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Fred A. Litwin Center for Cancer Genetics, Toronto, ON, M5G 1X5, Canada; University of Toronto, Department of Molecular Genetics, Toronto, ON, M5S 1A8, Canada
  • 9 University of California Irvine, Department of Medicine, Genetic Epidemiology Research Institute, Irvine, CA, 92617, USA
  • 10 Comprehensive Cancer Center Erlangen-EMN, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (FAU), Department of Gynecology and Obstetrics, Erlangen, 91054, Germany
  • 11 University of Helsinki, Department of Oncology, Helsinki University Hospital, Helsinki, 00290, Finland; Örebro University Hospital, Department of Oncology, Örebro, 70185, Sweden
  • 12 Copenhagen University Hospital, Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev, 2730, Denmark; Copenhagen University Hospital, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Herlev, 2730, Denmark; University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, 2200, Denmark
  • 13 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, CB1 8RN, UK
  • 14 IEO, European Institute of Oncology IRCCS, Division of Cancer Prevention and Genetics, Milan, 20141, Italy
  • 15 Universidad de La Sabana, Medical Faculty, Bogota, 140013, Colombia
  • 16 German Cancer Research Center (DKFZ), Molecular Epidemiology Group, C080, Heidelberg, 69120, Germany; University of Heidelberg, Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, Heidelberg, 69120, Germany
  • 17 University of Utah, Department of Internal Medicine and Huntsman Cancer Institute, Salt Lake City, UT, 84112, USA
  • 18 Instituto de Investigación Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Oncology and Genetics Unit, Vigo, 36312, Spain
  • 19 Seoul National University Graduate School, Department of Biomedical Sciences, Seoul, 03080, South Korea; Seoul National University, Cancer Research Institute, Seoul, 03080, South Korea; Seoul National University Medical Research Center, Institute of Health Policy and Management, Seoul, 03080, South Korea
  • 20 University of Sydney, Westmead Institute for Medical Research, Sydney, New South Wales, 2145, Australia
  • 21 Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, MN, 55905, USA
  • 22 University of Sheffield, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, Sheffield, S10 2TN, UK
  • 23 University of Sheffield, Academic Unit of Pathology, Department of Neuroscience, Sheffield, S10 2TN, UK
  • 24 Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, 171 65, Sweden
  • 25 Leiden University Medical Center, Department of Pathology, Leiden, 2333 ZA, the Netherlands; Leiden University Medical Center, Department of Human Genetics, Leiden, 2333 ZA, the Netherlands
  • 26 Hannover Medical School, Gynaecology Research Unit, Hannover, 30625, Germany
  • 27 University of Westminster, School of Life Sciences, London, W1B 2HW, UK
  • 28 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, CB1 8RN, UK; University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, CB1 8RN, UK
  • 29 University of Southampton, Faculty of Medicine, Southampton, SO17 1BJ, UK
  • 30 University Hospital Ulm, Department of Gynaecology and Obstetrics, Ulm, 89075, Germany
  • 31 University of Manchester, Manchester Academic Health Science Centre, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester, M13 9WL, UK; St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, North West Genomics Laboratory Hub, Manchester Centre for Genomic Medicine, Manchester, M13 9WL, UK
  • 32 National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, Bethesda, MD, 20850, USA; The University of Edinburgh, Usher Institute of Population Health Sciences and Informatics, Edinburgh, EH16 4UX, UK; The University of Edinburgh, Cancer Research UK Edinburgh Centre, Edinburgh, EH4 2XR, UK
  • 33 Leuven Cancer Institute, University Hospitals Leuven, Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven, 3000, Belgium
  • 34 Peter MacCallum Cancer Center, Melbourne, Victoria, Australia, 3000
  • 35 Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, 15706, Spain; University of California San Diego, Moores Cancer Center, La Jolla, CA, 92037, USA
  • 36 Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Medical Oncology Department, Hospital Clínico San Carlos, Madrid, 28040, Spain
  • 37 Spanish National Cancer Research Centre (CNIO), Human Cancer Genetics Programme, Madrid, 28029, Spain
  • 38 University of Southern California, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, CA, 90033, USA
  • 39 Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, 171 65, Sweden; Södersjukhuset, Department of Oncology, Stockholm, 118 83, Sweden
  • 40 German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, 69120, Germany
  • 41 University of Manchester, Manchester Academic Health Science Centre, Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, Manchester, M13 9PT, UK; Wythenshawe Hospital, Manchester University NHS Foundation Trust, Nightingale & Genesis Prevention Centre, Manchester, M23 9LT, UK; Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Unit, Manchester, M13 9WL, UK
  • 42 National University of Singapore and National University Health System, Saw Swee Hock School of Public Health, Singapore, 119077, Singapore; National University Health System, Department of Surgery, Singapore, 119228, Singapore
  • 43 Erasmus MC Cancer Institute, Department of Medical Oncology, Rotterdam, 3015 GD, the Netherlands
  • 44 Kaohsiung Municipal Hsiao-Kang Hospital, Department of Surgery, Kaohsiung, 812, Taiwan
  • 45 University of Manchester, Division of Cancer Sciences, Manchester, M13 9PL, UK
  • 46 University of Sydney, Australian Breast Cancer Tissue Bank, Westmead Institute for Medical Research, Sydney, New South Wales, 2145, Australia
  • 47 Peter MacCallum Cancer Center, Research Department, Melbourne, Victoria, Australia, 3000; The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, Victoria, 3000, Australia
  • 48 Aichi Cancer Center Research Institute, Division of Cancer Information and Control, Nagoya, 464-8681, Japan; Nagoya University Graduate School of Medicine, Division of Cancer Epidemiology, Nagoya, 466-8550, Japan
  • 49 Pomeranian Medical University, Department of Genetics and Pathology, Szczecin, 71-252, Poland; Pomeranian Medical University, Independent Laboratory of Molecular Biology and Genetic Diagnostics, Szczecin, 71-252, Poland
  • 50 Stanford University School of Medicine, Department of Epidemiology & Population Health, Stanford, CA, 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Department of Medicine, Division of Oncology, Stanford, CA, 94304, USA
  • 51 German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, 69120, Germany
  • 52 Seoul National University, Cancer Research Institute, Seoul, 03080, South Korea; Seoul National University College of Medicine, Department of Preventive Medicine, Seoul, 03080, South Korea
  • 53 Oslo University Hospital and University of Oslo, Department of Medical Genetics, Oslo, 0379, Norway; University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo, 0450, Norway
  • 54 Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong; The University of Hong Kong, Department of Surgery, Hong Kong; Hong Kong Sanatorium and Hospital, Department of Surgery and Cancer Genetics Center, Hong Kong
  • 55 VIB Center for Cancer Biology, VIB, Leuven, 3001, Belgium; University of Leuven, Laboratory for Translational Genetics, Department of Human Genetics, Leuven, 3000, Belgium
  • 56 Genome Institute of Singapore, Human Genetics Division, Singapore, 138672, Singapore
  • 57 Pomeranian Medical University, Department of Genetics and Pathology, Szczecin, 71-252, Poland
  • 58 Södersjukhuset, Department of Oncology, Stockholm, 118 83, Sweden; Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Stockholm, 118 83, Sweden
  • 59 Nagoya University Graduate School of Medicine, Division of Cancer Epidemiology, Nagoya, 466-8550, Japan; Aichi Cancer Center Research Institute, Division of Cancer Epidemiology and Prevention, Nagoya, 464-8681, Japan
  • 60 University of Malaya, Department of Surgery, Faculty of Medicine, Kuala Lumpur, 50603, Malaysia
  • 61 University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, ON, M5S 1A8, Canada; University Health Network, Laboratory Medicine Program, Toronto, ON, M5G 2C4, Canada
  • 62 University of Helsinki, Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, 00290, Finland
  • 63 Memorial Sloan Kettering Cancer Center, Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, New York, NY, 10065, USA; Memorial Sloan Kettering Cancer Center, Clinical Genetics Service, Department of Medicine, New York, NY, 10065, USA
  • 64 Spanish National Cancer Research Centre (CNIO), Human Cancer Genetics Programme, Madrid, 28029, Spain; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, 28029, Spain
  • 65 Seoul National University, Cancer Research Institute, Seoul, 03080, South Korea; Seoul National University College of Medicine, Department of Preventive Medicine, Seoul, 03080, South Korea; Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul, 03080, South Korea
  • 66 American Cancer Society, Department of Population Science, Atlanta, GA, 30303, USA
  • 67 University of Oulu, Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, Oulu, 90570, Finland; Northern Finland Laboratory Centre Oulu, Laboratory of Cancer Genetics and Tumor Biology, Oulu, 90570, Finland
  • 68 Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Milan, 20133, Italy
  • 69 Carmel Medical Center and Technion Faculty of Medicine, Clalit National Cancer Control Center, Haifa, 35254, Israel
  • 70 Hospital Universitario Puerta de Hierro, Medical Oncology Department, Madrid, 28222, Spain
  • 71 University Hospital of Larissa, Department of Oncology, Larissa, 411 10, Greece
  • 72 King's College London, School of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, London, UK
  • 73 University of Heidelberg, Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, Heidelberg, 69120, Germany; University Hospital and German Cancer Research Center, National Center for Tumor Diseases, Heidelberg, 69120, Germany
  • 74 The Institute of Cancer Research, Division of Genetics and Epidemiology, London, SM2 5NG, UK
  • 75 Academia Sinica, Institute of Biomedical Sciences, Taipei, 115, Taiwan; China Medical University, School of Public Health, Taichung, Taiwan
  • 76 University Hospital Heidelberg, Department of Pathology, Institute of Pathology, Heidelberg, 69120, Germany
  • 77 University of Auckland, Auckland, New Zealand
  • 78 University of Malaya, Department of Surgery, Faculty of Medicine, Kuala Lumpur, 50603, Malaysia; Cancer Research Malaysia, Breast Cancer Research Programme, Subang Jaya, Selangor, 47500, Malaysia
  • 79 German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, 69120, Germany; Pontificia Universidad Javeriana, Institute of Human Genetics, Bogota, 110231, Colombia
  • 80 Mayo Clinic, Department of Quantitative Health Sciences, Division of Epidemiology, Rochester, MN, 55905, USA
  • 81 Erasmus University Medical Center, Department of Pathology, Rotterdam, 3015 CN, the Netherlands
  • 82 Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Stockholm, 118 83, Sweden
  • 83 The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam, 1066 CX, the Netherlands; The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Psychosocial Research and Epidemiology, Amsterdam, 1066 CX, the Netherlands
Eur J Cancer, 2022 Sep;173:178-193.
PMID: 35933885 DOI: 10.1016/j.ejca.2022.06.011

Abstract

BACKGROUND: Predict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).

METHOD: The prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.

RESULTS: Having a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0.902 for patients with ER-positive tumours (p = 2.3 × 10-6) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted.

CONCLUSION: The inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predictions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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