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Breast Cancer Risk Factors and Survival by Tumor Subtype: Pooled Analyses from the Breast Cancer Association Consortium

Morra A 1 , Jung AY 2 , Behrens S 2 , Keeman R 1 , Ahearn TU 3 , Anton-Culver H 4 Show all authors , Arndt V 5 , Augustinsson A 6 , Auvinen PK 7 , Beane Freeman LE 3 , Becher H 8 , Beckmann MW 9 , Blomqvist C 10 , Bojesen SE 11 , Bolla MK 12 , Brenner H 5 , Briceno I 13 , Brucker SY 14 , Camp NJ 15 , Campa D 2 , Canzian F 16 , Castelao JE 17 , Chanock SJ 3 , Choi JY 18 , Clarke CL , Couch FJ 19 , Cox A 20 , Cross SS 21 , Czene K 22 , Dörk T 23 , Dunning AM 24 , Dwek M 25 , Easton DF 12 , Eccles DM 26 , Egan KM 27 , Evans DG 28 , Fasching PA 9 , Flyger H 29 , Gago-Dominguez M 30 , Gapstur SM 31 , García-Sáenz JA 32 , Gaudet MM 31 , Giles GG 33 , Grip M 34 , Guénel P 35 , Haiman CA 36 , Håkansson N 37 , Hall P 22 , Hamann U 38 , Han SN 39 , Hart SN 40 , Hartman M 41 , Heyworth JS 42 , Hoppe R 43 , Hopper JL 44 , Hunter DJ 45 , Ito H 46 , Jager A 47 , Jakimovska M 48 , Jakubowska A 49 , Janni W 50 , Kaaks R 2 , Kang D 18 , Kapoor PM 2 , Kitahara CM 51 , Koutros S 3 , Kraft P 52 , Kristensen VN , Lacey JV 53 , Lambrechts D 54 , Le Marchand L 55 , Li J 56 , Lindblom A 57 , Lubiński J 49 , Lush M 12 , Mannermaa A 7 , Manoochehri M 38 , Margolin S 58 , Mariapun S 59 , Matsuo K 46 , Mavroudis D 60 , Milne RL 33 , Muranen TA 61 , Newman WG 28 , Noh DY 62 , Nordestgaard BG 11 , Obi N 63 , Olshan AF 64 , Olsson H 6 , Park-Simon TW 23 , Petridis C 65 , Pharoah PDP 12 , Plaseska-Karanfilska D 48 , Presneau N 25 , Rashid MU 38 , Rennert G 66 , Rennert HS 66 , Rhenius V 24 , Romero A 67 , Saloustros E 68 , Sawyer EJ 69 , Schneeweiss A 70 , Schwentner L 50 , Scott C 40 , Shah M 24 , Shen CY 71 , Shu XO 72 , Southey MC 33 , Stram DO 36 , Tamimi RM 52 , Tapper W 26 , Tollenaar RAEM 73 , Tomlinson I 74 , Torres D 38 , Troester MA 64 , Truong T 35 , Vachon CM 75 , Wang Q 12 , Wang SS 53 , Williams JA 15 , Winqvist R 76 , Wolk A 37 , Wu AH 36 , Yoo KY 77 , Yu JC 78 , Zheng W 72 , Ziogas A 4 , Yang XR 3 , Eliassen AH 52 , Holmes MD 52 , García-Closas M 3 , Teo SH 59 , Schmidt MK 79 , Chang-Claude J 2 , ABCTB Investigators , NBCS Collaborators

Affiliations 

  • 1 Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
  • 2 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 3 National Cancer Institute, NIH, Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, Bethesda, Maryland
  • 4 Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, California
  • 5 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 6 Clinical Sciences, Department of Cancer Epidemiology, Lund University, Lund, Sweden
  • 7 Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland
  • 8 Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 9 Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
  • 10 Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  • 11 Copenhagen University Hospital, Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev, Denmark
  • 12 Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United Kingdom
  • 13 Medical Faculty, Universidad de La Sabana, Bogota, Colombia
  • 14 Department of Gynecology and Obstetrics, University of Tübingen, Tübingen, Germany
  • 15 Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
  • 16 Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 17 Oncology and Genetics Unit, Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Investigacion Sanitaria Galicia Sur (IISGS), Vigo, Spain
  • 18 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea
  • 19 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
  • 20 Department of Oncology and Metabolism, Sheffield Institute for Nucleic Acids (SInFoNiA), University of Sheffield, Sheffield, United Kingdom
  • 21 Department of Neuroscience, Academic Unit of Pathology, University of Sheffield, Sheffield, United Kingdom
  • 22 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 23 Gynaecology Research Unit, Hannover Medical School, Hannover, Germany
  • 24 Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United Kingdom
  • 25 School of Life Sciences, University of Westminster, London, United Kingdom
  • 26 Faculty of Medicine, University of Southampton, Southampton, United Kingdom
  • 27 Division of Population Sciences, Moffitt Cancer Center & Research Institute, Tampa, Florida
  • 28 Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
  • 29 Copenhagen University Hospital, Department of Breast Surgery, Herlev and Gentofte Hospital, Herlev, Denmark
  • 30 Galician Public Foundation of Genomic Medicine (FPGMX), Genomic Medicine Group, International Cancer Genetics and Epidemiology Group, Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
  • 31 Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
  • 32 Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain
  • 33 Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
  • 34 Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
  • 35 Center for Research in Epidemiology and Population Health (CESP), Team Exposome and Heredity, INSERM, University Paris-Saclay, Villejuif, France
  • 36 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
  • 37 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  • 38 German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, Germany
  • 39 Department of Gynaecological Oncology, Leuven Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
  • 40 Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
  • 41 Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
  • 42 School of Population and Global Health, The University of Western Australia, Perth, Western Australia, Australia
  • 43 Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany
  • 44 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
  • 45 University of Oxford, Nuffield Department of Population Health, Oxford, United Kingdom
  • 46 Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 47 Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
  • 48 MASA, Research Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', Skopje, Republic of North Macedonia
  • 49 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
  • 50 Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany
  • 51 Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
  • 52 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
  • 53 Department of Computational and Quantitative Medicine, City of Hope, Duarte, California
  • 54 VIB Center for Cancer Biology, Leuven, Belgium
  • 55 Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
  • 56 Human Genetics Division, Genome Institute of Singapore, Singapore, Singapore
  • 57 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  • 58 Department of Oncology, Södersjukhuset, Stockholm, Sweden
  • 59 Breast Cancer Research Programme, Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia
  • 60 Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece
  • 61 Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  • 62 Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
  • 63 Institute for Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 64 Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • 65 Research Oncology, King's College London, Guy's Hospital, London, United Kingdom
  • 66 Carmel Medical Center and Technion Faculty of Medicine, Clalit National Cancer Control Center, Haifa, Israel
  • 67 Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain
  • 68 Department of Oncology, University Hospital of Larissa, Larissa, Greece
  • 69 School of Cancer & Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, King's College London, London, United Kingdom
  • 70 National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany
  • 71 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
  • 72 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 73 Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
  • 74 Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom
  • 75 Division of Epidemiology, Department of Health Science Research, Mayo Clinic, Rochester, Minnesota
  • 76 Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland
  • 77 Seoul National University College of Medicine, Seoul, Korea
  • 78 Department of Surgery, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
  • 79 Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands. mk.schmidt@nki.nl
Cancer Epidemiol Biomarkers Prev, 2021 Apr;30(4):623-642.
PMID: 33500318 DOI: 10.1158/1055-9965.EPI-20-0924

Abstract

BACKGROUND: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.

METHODS: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.

RESULTS: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (P adj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking.

CONCLUSIONS: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype.

IMPACT: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

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

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