International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts

Author:

Timmins Iain R.12ORCID,Jones Michael E.1,O'Brien Katie M.3ORCID,Adami Hans-Olov45ORCID,Aune Dagfinn678ORCID,Baglietto Laura9ORCID,Bertrand Kimberly A.10ORCID,Brantley Kristen D.11ORCID,Chen Yu12,Clague DeHart Jessica13ORCID,Clendenen Tess V.12ORCID,Dossus Laure14ORCID,Eliassen A. Heather1115ORCID,Fletcher Olivia16ORCID,Fournier Agnès17ORCID,Håkansson Niclas18ORCID,Hankinson Susan E.19,Houlston Richard S.1ORCID,Joshu Corinne E.20ORCID,Kirsh Victoria A.2122ORCID,Kitahara Cari M.23ORCID,Koh Woon-Puay2425,Linet Martha S.23ORCID,Park Hannah Lui26ORCID,Lynch Brigid M.272829ORCID,May Anne M.30ORCID,Mellemkjær Lene31ORCID,Milne Roger L.272832ORCID,Palmer Julie R.10ORCID,Ricceri Fulvio3334,Rohan Thomas E.35,Ruddy Kathryn J.36ORCID,Sánchez Maria-Jose37383940ORCID,Shu Xiao-Ou41ORCID,Smith-Byrne Karl42,Steindorf Karen43ORCID,Sund Malin4445ORCID,Vachon Celine M.46ORCID,Vatten Lars J.47ORCID,Visvanathan Kala20ORCID,Weiderpass Elisabete48ORCID,Willett Walter C.1115ORCID,Wolk Alicja18ORCID,Yuan Jian-Min4950,Zheng Wei41ORCID,Nichols Hazel B.51ORCID,Sandler Dale P.3ORCID,Swerdlow Anthony J.152,Schoemaker Minouk J.153

Affiliation:

1. Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom

2. Statistical Innovation, AstraZeneca, Cambridge, United Kingdom

3. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC

4. Clinical Effectiveness Group, Institute of Health and Society, University of Oslo, Oslo, Norway

5. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

6. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom

7. Department of Nutrition, Oslo New University College, Oslo, Norway

8. Department of Research, The Cancer Registry of Norway, Oslo, Norway

9. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

10. Slone Epidemiology Center at Boston University, Boston, MA

11. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA

12. Division of Epidemiology, Department of Population Health, NYU Grossman School of Medicine, New York, NY

13. School of Community and Global Health, Claremont Graduate University, Claremont, CA

14. Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France

15. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

16. The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom

17. UVSQ, CESP, Gustave Roussy, Team “Exposome, Heredity, Cancer, and Health”, INSERM, Paris-Saclay University, Paris-South University, Villejuif, France

18. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

19. Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA

20. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

21. Ontario Institute for Cancer Research, Toronto, ON, Canada

22. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

23. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD

24. Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

25. Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore, Singapore

26. Department of Pathology and Laboratory Medicine, Department of Epidemiology, UC Irvine School of Medicine, Irvine, CA

27. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia

28. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia

29. Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia

30. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

31. Danish Cancer Society Research Center, Copenhagen, Denmark

32. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia

33. Department of Clinical and Biological Sciences, Centre for Biostatistics, Epidemiology, and Public Health, University of Turin, Turin, Italy

34. Unit of Epidemiology, Regional Health Service ASL TO3, Turin, Italy

35. Albert Einstein College of Medicine, Bronx, NY

36. Department of Oncology, Mayo Clinic, Rochester, MN

37. Escuela Andaluza de Salud Pública (EASP), Granada, Spain

38. Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain

39. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

40. Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain

41. Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN

42. Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom

43. Division of Physical Activity, Prevention and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

44. Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Umeâ, Sweden

45. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

46. Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN

47. Department of Public Health and Nursing, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway

48. International Agency for Research on Cancer, World Health Organization, Lyon, France

49. Division of Cancer Control and Population Sciences, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA

50. Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA

51. Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC

52. Division of Breast Cancer Research, The Institute of Cancer Research, London, United Kingdom

53. Real World Solutions, IQVIA, Amsterdam, the Netherlands

Abstract

PURPOSE There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. METHODS We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. RESULTS Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship ( Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2–enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity. CONCLUSION This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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