BMI and breast cancer risk around age at menopause

doi:10.1016/j.canep.2024.102545

. 2024 Apr:89:102545.

doi: 10.1016/j.canep.2024.102545. Epub 2024 Feb 19.

BMI and breast cancer risk around age at menopause

Ann Von Holle¹, Hans-Olov Adami², Laura Baglietto³, Amy Berrington de Gonzalez⁴, Kimberly A Bertrand⁵, William Blot⁶, Yu Chen⁷, Jessica Clague DeHart⁸, Laure Dossus⁹, A Heather Eliassen¹⁰, Agnes Fournier¹¹, Montse Garcia-Closas⁴, Graham Giles¹², Marcela Guevara¹³, Susan E Hankinson¹⁴, Alicia Heath¹⁵, Michael E Jones⁴, Corinne E Joshu¹⁶, Rudolf Kaaks¹⁷, Victoria A Kirsh¹⁸, Cari M Kitahara¹⁹, Woon-Puay Koh²⁰, Martha S Linet¹⁹, Hannah Lui Park²¹, Giovanna Masala²², Lene Mellemkjaer²³, Roger L Milne²⁴, Katie M O'Brien²⁵, Julie R Palmer⁵, Elio Riboli¹⁵, Thomas E Rohan²⁶, Martha J Shrubsole⁶, Malin Sund²⁷, Rulla Tamimi²⁸, Sandar Tin Tin²⁹, Kala Visvanathan¹⁶, Roel Ch Vermeulen³⁰, Elisabete Weiderpass³¹, Walter C Willett³², Jian-Min Yuan³³, Anne Zeleniuch-Jacquotte³⁴, Hazel B Nichols³⁵, Dale P Sandler²⁵, Anthony J Swerdlow³⁶, Minouk J Schoemaker³⁷, Clarice R Weinberg³⁸

Affiliations

¹ Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
² Clinical Effectiveness Group, Institute of Health and Society, University of Oslo, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinksa Institutet, Stockholm, Sweden.
³ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
⁴ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
⁵ Slone Epidemiology Center, Boston University, Boston, MA, USA.
⁶ Vanderbilt University Medical Center, Nashville, TN, USA.
⁷ Division of Epidemiology, Department of Population Health, NYU Grossman School of Medicine, New York, NY, USA.
⁸ School of Community and Global Health, Claremont Graduate University, Claremont, CA, USA.
⁹ Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
¹⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Centre for Research in Epidemiology and Statistics, Paris, France.
¹² Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
¹³ Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain.
¹⁴ Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.
¹⁵ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
¹⁶ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹⁷ Division of Cancer Epidemiology, German Cancer Research Center, DKFZ, Heidelberg, Germany.
¹⁸ Ontario Institute for Cancer Research, Toronto, ON, Canada.
¹⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
²⁰ Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore.
²¹ Department of Pathology and Laboratory Medicine, Department of Epidemiology, UC Irvine School of Medicine, Irvine, CA, USA.
²² Institute for the Study and Prevention of Cancer, Florence, Italy.
²³ Diet, Cancer and Health, Danish Cancer Institute, Copenhagen, Denmark.
²⁴ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
²⁵ Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
²⁶ Albert Einstein College of Medicine, Bronx, NY, USA.
²⁷ Department of Surgical and perioperative Sciences/Surgery, Umea University, Sweden.
²⁸ Department of Population Health Sciences, Weill Cornell Medical College, NY, USA.
²⁹ Cancer Epidemiology Unit, Oxford Population Health, University of Oxford, United Kingdom.
³⁰ Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.
³¹ International Agency for Research on Cancer, World Health Organization, Lyon, France.
³² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
³³ Division of Cancer Control and Population Science, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, USA; Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
³⁴ Department of Population Health, NYU Grossman School of Medicine, NY, USA.
³⁵ Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA.
³⁶ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom; Division of Breast Cancer Research, The Institute of Cancer Research, London, United Kingdom.
³⁷ Real World Solutions, IQVIA, the Netherlands.
³⁸ Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Electronic address: [email protected].

PMID: 38377945
PMCID: PMC10942753 (available on 2025-04-01)
DOI: 10.1016/j.canep.2024.102545

BMI and breast cancer risk around age at menopause

Ann Von Holle et al. Cancer Epidemiol. 2024 Apr.

. 2024 Apr:89:102545.

doi: 10.1016/j.canep.2024.102545. Epub 2024 Feb 19.

Authors

Affiliations

¹ Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
² Clinical Effectiveness Group, Institute of Health and Society, University of Oslo, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinksa Institutet, Stockholm, Sweden.
³ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
⁴ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
⁵ Slone Epidemiology Center, Boston University, Boston, MA, USA.
⁶ Vanderbilt University Medical Center, Nashville, TN, USA.
⁷ Division of Epidemiology, Department of Population Health, NYU Grossman School of Medicine, New York, NY, USA.
⁸ School of Community and Global Health, Claremont Graduate University, Claremont, CA, USA.
⁹ Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
¹⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Centre for Research in Epidemiology and Statistics, Paris, France.
¹² Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
¹³ Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain.
¹⁴ Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.
¹⁵ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
¹⁶ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹⁷ Division of Cancer Epidemiology, German Cancer Research Center, DKFZ, Heidelberg, Germany.
¹⁸ Ontario Institute for Cancer Research, Toronto, ON, Canada.
¹⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
²⁰ Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore.
²¹ Department of Pathology and Laboratory Medicine, Department of Epidemiology, UC Irvine School of Medicine, Irvine, CA, USA.
²² Institute for the Study and Prevention of Cancer, Florence, Italy.
²³ Diet, Cancer and Health, Danish Cancer Institute, Copenhagen, Denmark.
²⁴ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
²⁵ Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
²⁶ Albert Einstein College of Medicine, Bronx, NY, USA.
²⁷ Department of Surgical and perioperative Sciences/Surgery, Umea University, Sweden.
²⁸ Department of Population Health Sciences, Weill Cornell Medical College, NY, USA.
²⁹ Cancer Epidemiology Unit, Oxford Population Health, University of Oxford, United Kingdom.
³⁰ Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.
³¹ International Agency for Research on Cancer, World Health Organization, Lyon, France.
³² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
³³ Division of Cancer Control and Population Science, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, USA; Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
³⁴ Department of Population Health, NYU Grossman School of Medicine, NY, USA.
³⁵ Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA.
³⁶ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom; Division of Breast Cancer Research, The Institute of Cancer Research, London, United Kingdom.
³⁷ Real World Solutions, IQVIA, the Netherlands.
³⁸ Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Electronic address: [email protected].

PMID: 38377945
PMCID: PMC10942753 (available on 2025-04-01)
DOI: 10.1016/j.canep.2024.102545

Abstract

Background: A high body mass index (BMI, kg/m²) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology.

Methods: We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy.

Results: The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO.

Conclusion: The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55.

Keywords: Body mass index; Breast neoplasms; Middle aged; Postmenopause; Premenopause.

Published by Elsevier Ltd.

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Conflict of interest statement

Declaration of Competing Interest none.

References

1. García-Estévez L, Cortés J, Pérez S, Calvo I, Gallegos I, Moreno-Bueno G. Obesity and Breast Cancer: A Paradoxical and Controversial Relationship Influenced by Menopausal Status. Frontiers in Oncology. 2021;11:3114. doi:10.3389/fonc.2021.705911 - DOI - PMC - PubMed
1. Bergström A, Pisani P, Tenet V, Wolk A, Adami HO. Overweight as an avoidable cause of cancer in Europe. International Journal of Cancer. 2001;91(3):421–430. doi:10.1002/1097-0215(200002)9999:9999<::AID-IJC1053>3.0.CO;2-T - DOI - PubMed
1. Berstad P, Coates RJ, Bernstein L, et al. A case-control study of body mass index and breast cancer risk in white and African-American women. Cancer Epidemiol Biomarkers Prev. 2010;19(6):1532–1544. doi:10.1158/1055-9965.EPI-10-0025 - DOI - PMC - PubMed
1. Harris HR, Willett WC, Terry KL, Michels KB. Body Fat Distribution and Risk of Premenopausal Breast Cancer in the Nurses’ Health Study II. JNCI: Journal of the National Cancer Institute. 2011;103(3):273–278. doi:10.1093/jnci/djq500 - DOI - PMC - PubMed
1. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet. 2008;371(9612):569–578. doi:10.1016/S0140-6736(08)60269-X - DOI - PubMed

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[1] García-Estévez L, Cortés J, Pérez S, Calvo I, Gallegos I, Moreno-Bueno G. Obesity and Breast Cancer: A Paradoxical and Controversial Relationship Influenced by Menopausal Status. Frontiers in Oncology. 2021;11:3114. doi:10.3389/fonc.2021.705911 - DOI - PMC - PubMed

[2] García-Estévez L, Cortés J, Pérez S, Calvo I, Gallegos I, Moreno-Bueno G. Obesity and Breast Cancer: A Paradoxical and Controversial Relationship Influenced by Menopausal Status. Frontiers in Oncology. 2021;11:3114. doi:10.3389/fonc.2021.705911 - DOI - PMC - PubMed

[3] Bergström A, Pisani P, Tenet V, Wolk A, Adami HO. Overweight as an avoidable cause of cancer in Europe. International Journal of Cancer. 2001;91(3):421–430. doi:10.1002/1097-0215(200002)9999:9999<::AID-IJC1053>3.0.CO;2-T - DOI - PubMed

[4] Bergström A, Pisani P, Tenet V, Wolk A, Adami HO. Overweight as an avoidable cause of cancer in Europe. International Journal of Cancer. 2001;91(3):421–430. doi:10.1002/1097-0215(200002)9999:9999<::AID-IJC1053>3.0.CO;2-T - DOI - PubMed

[5] Berstad P, Coates RJ, Bernstein L, et al. A case-control study of body mass index and breast cancer risk in white and African-American women. Cancer Epidemiol Biomarkers Prev. 2010;19(6):1532–1544. doi:10.1158/1055-9965.EPI-10-0025 - DOI - PMC - PubMed

[6] Berstad P, Coates RJ, Bernstein L, et al. A case-control study of body mass index and breast cancer risk in white and African-American women. Cancer Epidemiol Biomarkers Prev. 2010;19(6):1532–1544. doi:10.1158/1055-9965.EPI-10-0025 - DOI - PMC - PubMed

[7] Harris HR, Willett WC, Terry KL, Michels KB. Body Fat Distribution and Risk of Premenopausal Breast Cancer in the Nurses’ Health Study II. JNCI: Journal of the National Cancer Institute. 2011;103(3):273–278. doi:10.1093/jnci/djq500 - DOI - PMC - PubMed

[8] Harris HR, Willett WC, Terry KL, Michels KB. Body Fat Distribution and Risk of Premenopausal Breast Cancer in the Nurses’ Health Study II. JNCI: Journal of the National Cancer Institute. 2011;103(3):273–278. doi:10.1093/jnci/djq500 - DOI - PMC - PubMed

[9] Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet. 2008;371(9612):569–578. doi:10.1016/S0140-6736(08)60269-X - DOI - PubMed

[10] Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. The Lancet. 2008;371(9612):569–578. doi:10.1016/S0140-6736(08)60269-X - DOI - PubMed

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BMI and breast cancer risk around age at menopause

Affiliations

BMI and breast cancer risk around age at menopause

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