Article open access publication

Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women

JAMA Oncology, American Medical Association (AMA), ISSN 2374-2445

Volume 4, 11, 2018

DOI:10.1001/jamaoncol.2018.1771, Dimensions: pub.1105032743, PMC: PMC6248078, PMID: 29931120,



  1. (1) Institute of Cancer Research, grid.18886.3f
  2. (2) University of North Carolina at Chapel Hill, grid.10698.36
  3. (3) National Institute of Environmental Health Sciences, grid.280664.e
  4. (4) Harvard University, grid.38142.3c
  5. (5) Karolinska Institute, grid.4714.6
  6. (6) University of Pisa, grid.5395.a
  7. (7) City Of Hope National Medical Center, grid.410425.6
  8. (8) Boston University, grid.189504.1
  9. (9) University of Paris-Sud, grid.5842.b
  10. (10) The Arctic University of Norway, grid.10919.30
  11. (11) New York University, grid.137628.9
  12. (12) Johns Hopkins University, grid.21107.35
  13. (13) Public Health Direction and Biodonostia Research Institute and Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Basque Regional Health Department, San Sebastian, Spain
  14. (14) International Agency For Research On Cancer, grid.17703.32
  15. (15) Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  16. (16) Cancer Council Victoria, grid.3263.4
  17. (17) University of Melbourne, grid.1008.9
  18. (18) Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst
  19. (19) German Cancer Research Center, grid.7497.d
  20. (20) University of Oxford, grid.4991.5
  21. (21) University of Toronto, grid.17063.33
  22. (22) National Cancer Institute, grid.48336.3a
  23. (23) National University of Singapore, grid.4280.e
  24. (24) Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy
  25. (25) Imperial College London, grid.7445.2
  26. (26) Aarhus University, grid.7048.b, AU
  27. (27) Radiation Effects Research Foundation, grid.418889.4
  28. (28) University Medical Center, Utrecht University, Utrecht, the Netherlands
  29. (29) Albert Einstein College of Medicine, grid.251993.5
  30. (30) Umeå University, grid.12650.30
  31. (31) Hellenic Health Foundation, grid.424637.0
  32. (32) University of Oslo, grid.5510.1
  33. (33) University of Southern California, grid.42505.36
  34. (34) Cancer Registry of Norway, grid.418941.1
  35. (35) Norwegian University of Science and Technology, grid.5947.f
  36. (36) University of Helsinki, grid.7737.4
  37. (37) University of Pittsburgh, grid.21925.3d


Importance: The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. Objective: To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. Design, Setting, and Participants: This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017. Exposures: Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years. Main Outcomes and Measures: Invasive or in situ premenopausal breast cancer. Results: Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall. Conclusions and Relevance: The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.


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2018: Realized

Research area: Medicine

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2018: Level 1

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Times Cited: 62

Field Citation Ratio (FCR): 38.91

Relative Citation ratio (RCR): 8.13

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