BMI and breast cancer risk around age at menopause

Ann Von Holle; Hans-Olov Adami; Laura Baglietto; Amy Berrington; Kimberly A Bertrand; William Blot; Yu Chen; Jessica Clague DeHart; Laure Dossus; A Heather Eliassen; Agnes Fournier; Montse Garcia-Closas; Graham Giles; Marcela Guevara; Susan E Hankinson; Alicia Heath; Michael E Jones; Corinne E Joshu; Rudolf Kaaks; Victoria A Kirsh; Cari M Kitahara; Woon-Puay Koh; Martha S Linet; Hannah Lui Park; Giovanna Masala; Lene Mellemkjaer; Roger L Milne; Katie M O'Brien; Julie R Palmer; Elio Riboli; Thomas E Rohan; Martha J Shrubsole; Malin Sund; Rulla Tamimi; Sandar Tin Tin; Kala Visvanathan; Roel Ch Vermeulen; Elisabete Weiderpass; Walter C Willett; Jian-Min Yuan; Anne Zeleniuch-Jacquotte; Hazel B Nichols; Dale P Sandler; Anthony J Swerdlow; Minouk J Schoemaker; Clarice R Weinberg

doi:10.1016/j.canep.2024.102545

BMI and breast cancer risk around age at menopause

Ann Von Holle, Hans-Olov Adami, Laura Baglietto, Amy Berrington, Kimberly A Bertrand, William Blot, Yu Chen, Jessica Clague DeHart, Laure Dossus, A Heather Eliassen, Agnes Fournier, Montse Garcia-Closas, Graham Giles, Marcela Guevara, Susan E Hankinson, Alicia Heath, Michael E Jones, Corinne E Joshu, Rudolf Kaaks, Victoria A KirshCari M Kitahara, Woon-Puay Koh, Martha S Linet, Hannah Lui Park, Giovanna Masala, Lene Mellemkjaer, Roger L Milne, Katie M O'Brien, Julie R Palmer, Elio Riboli, Thomas E Rohan, Martha J Shrubsole, Malin Sund, Rulla Tamimi, Sandar Tin Tin, Kala Visvanathan, Roel Ch Vermeulen, Elisabete Weiderpass, Walter C Willett, Jian-Min Yuan, Anne Zeleniuch-Jacquotte, Hazel B Nichols, Dale P Sandler, Anthony J Swerdlow, Minouk J Schoemaker, Clarice R Weinberg^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: A high body mass index (BMI, kg/m 2) 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.

Original language	English
Article number	102545
Number of pages	8
Journal	Cancer Epidemiology
Volume	89
Early online date	19 Feb 2024
DOIs	https://doi.org/10.1016/j.canep.2024.102545
Publication status	Published - Apr 2024

Bibliographical note

Publisher Copyright:
© 2024

Funding

We would like to thank Dr. Shanshan Zhao and Dr. Christine R. Langton for their critical review of the manuscript. The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR) and/or the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: AL, AR, AZ, CA, CO, CT, DE, DC, FL, GA, HI, IA, IL, IN, KY, LA, MD, MA, MI, MO, MS, NE, NJ, NM, NY, NC, OH, OK, OR, PA, SC, TN, TX, VA, WA, WI. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. Department of Health and Human Services, the National Institutes of Health, the National Cancer Institute, or the state cancer registries. We thank participants and staff of the BWHS for their contributions. This study was supported by the Division of Intramural Research at NIEHS, in the National Institutes of Health, under projects Z01-ES044005 for D.P. Sandler and Z01-ES102245 for C.R. Weinberg. This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The Black Women's Health Study was supported by NIH grants (No. R01-CA058420 and U01-CA164974). The Sister Study was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (project Z01-ES044005 to DPS) which also partially supported the PMBCCG. The Singapore Chinese Health Study was supported by NIH grants (No. R01-CA144034 and UM1-CA182876). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom); The Generations Study is supported by Breast Cancer Now and The Institute of Cancer Research, United Kingdom. Thomas E. Rohan is supported in part by the Breast Cancer Research Foundation (BCRF-22-140). This study was supported by the Division of Intramural Research at NIEHS, in the National Institutes of Health , under projects Z01-ES044005 for D.P. Sandler and Z01-ES102245 for C.R. Weinberg. This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The Black Women’s Health Study was supported by NIH grants (No. R01-CA058420 and U01-CA164974 ). The Sister Study was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (project Z01-ES044005 to DPS) which also partially supported the PMBCCG. The Singapore Chinese Health Study was supported by NIH grants (No. R01-CA144034 and UM1-CA182876 ). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom); The Generations Study is supported by Breast Cancer Now and The Institute of Cancer Research, United Kingdom . Thomas E. Rohan is supported in part by the Breast Cancer Research Foundation ( BCRF-22-140 ). The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) and/or the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: AL, AR, AZ, CA, CO, CT, DE, DC, FL, GA, HI, IA, IL, IN, KY, LA, MD, MA, MI, MO, MS, NE, NJ, NM, NY, NC, OH, OK, OR, PA, SC, TN, TX, VA, WA, WI. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. Department of Health and Human Services, the National Institutes of Health, the National Cancer Institute, or the state cancer registries. We thank participants and staff of the BWHS for their contributions.

Funders	Funder number
BWHS
Catalan Institute of Oncology - ICO
Compagnia di SanPaolo
County Councils of Skåne
Dutch Prevention Funds
Dutch ZON (Zorg Onderzoek Nederland
FIS
German Institute of Human Nutrition Potsdam-Rehbruecke
Health Research Fund
LK Research Funds
NKR
Netherlands Cancer Registry
National Institutes of Health	R01-CA058420, U01-CA164974
National Institutes of Health
U.S. Department of Health and Human Services
National Cancer Institute
National Institute of Environmental Health Sciences	UM1-CA182876, Z01-ES044005, Z01-ES102245, R01-CA144034
National Institute of Environmental Health Sciences
Cancer Research Institute
Breast Cancer Research Foundation	BCRF-22-140
Breast Cancer Research Foundation
Division of Intramural Research
Kræftens Bekæmpelse
Deutsches Krebsforschungszentrum
Centre International de Recherche sur le Cancer
National Research Council
University of Maryland School of Public Health
Department of Epidemiology and Biostatistics, University of California, San Francisco
Medical Research Council	MR/M012190/1
Medical Research Council
Cancer Research UK	C8221/A29017
Cancer Research UK
World Cancer Research Fund
Imperial College London
Institut national de la santé et de la recherche médicale
Bundesministerium für Bildung und Forschung
Cancerfonden
Ministerie van Volksgezondheid, Welzijn en Sport
Ligue Contre le Cancer
Vetenskapsrådet
Instituto de Salud Carlos III
Associazione Italiana per la Ricerca sul Cancro
Deutsche Krebshilfe
Breast Cancer Now
Institut Gustave-Roussy
Mutuelle Générale de l'Education Nationale
Consejería de Salud y Familias, Junta de Andalucía
NIHR Imperial Biomedical Research Centre

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10.1016/j.canep.2024.102545

1-s2.0-S1877782124000249-mainFinal published version, 464 KBLicence: Taverne

Cite this

Von Holle, A., Adami, H.-O., Baglietto, L., Berrington, A., Bertrand, K. A., Blot, W., Chen, Y., DeHart, J. C., Dossus, L., Eliassen, A. H., Fournier, A., Garcia-Closas, M., Giles, G., Guevara, M., Hankinson, S. E., Heath, A., Jones, M. E., Joshu, C. E., Kaaks, R., ... Weinberg, C. R. (2024). BMI and breast cancer risk around age at menopause. Cancer Epidemiology, 89, Article 102545. https://doi.org/10.1016/j.canep.2024.102545

@article{58d2fd23bb804bfb9a6c52e0b41f0aea,

title = "BMI and breast cancer risk around age at menopause",

abstract = "BACKGROUND: A high body mass index (BMI, kg/m 2) 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.",

author = "\{Von Holle\}, Ann and Hans-Olov Adami and Laura Baglietto and Amy Berrington and Bertrand, \{Kimberly A\} and William Blot and Yu Chen and DeHart, \{Jessica Clague\} and Laure Dossus and Eliassen, \{A Heather\} and Agnes Fournier and Montse Garcia-Closas and Graham Giles and Marcela Guevara and Hankinson, \{Susan E\} and Alicia Heath and Jones, \{Michael E\} and Joshu, \{Corinne E\} and Rudolf Kaaks and Kirsh, \{Victoria A\} and Kitahara, \{Cari M\} and Woon-Puay Koh and Linet, \{Martha S\} and Park, \{Hannah Lui\} and Giovanna Masala and Lene Mellemkjaer and Milne, \{Roger L\} and O'Brien, \{Katie M\} and Palmer, \{Julie R\} and Elio Riboli and Rohan, \{Thomas E\} and Shrubsole, \{Martha J\} and Malin Sund and Rulla Tamimi and \{Tin Tin\}, Sandar and Kala Visvanathan and Vermeulen, \{Roel Ch\} and Elisabete Weiderpass and Willett, \{Walter C\} and Jian-Min Yuan and Anne Zeleniuch-Jacquotte and Nichols, \{Hazel B\} and Sandler, \{Dale P\} and Swerdlow, \{Anthony J\} and Schoemaker, \{Minouk J\} and Weinberg, \{Clarice R\}",

note = "Publisher Copyright: {\textcopyright} 2024",

year = "2024",

month = apr,

doi = "10.1016/j.canep.2024.102545",

language = "English",

volume = "89",

journal = "Cancer Epidemiology",

issn = "1877-7821",

publisher = "Elsevier Ltd",

}

Von Holle, A, Adami, H-O, Baglietto, L, Berrington, A, Bertrand, KA, Blot, W, Chen, Y, DeHart, JC, Dossus, L, Eliassen, AH, Fournier, A, Garcia-Closas, M, Giles, G, Guevara, M, Hankinson, SE, Heath, A, Jones, ME, Joshu, CE, Kaaks, R, Kirsh, VA, Kitahara, CM, Koh, W-P, Linet, MS, Park, HL, Masala, G, Mellemkjaer, L, Milne, RL, O'Brien, KM, Palmer, JR, Riboli, E, Rohan, TE, Shrubsole, MJ, Sund, M, Tamimi, R, Tin Tin, S, Visvanathan, K, Vermeulen, RC, Weiderpass, E, Willett, WC, Yuan, J-M, Zeleniuch-Jacquotte, A, Nichols, HB, Sandler, DP, Swerdlow, AJ, Schoemaker, MJ & Weinberg, CR 2024, 'BMI and breast cancer risk around age at menopause', Cancer Epidemiology, vol. 89, 102545. https://doi.org/10.1016/j.canep.2024.102545

TY - JOUR

T1 - BMI and breast cancer risk around age at menopause

AU - Von Holle, Ann

AU - Adami, Hans-Olov

AU - Baglietto, Laura

AU - Berrington, Amy

AU - Bertrand, Kimberly A

AU - Blot, William

AU - Chen, Yu

AU - DeHart, Jessica Clague

AU - Dossus, Laure

AU - Eliassen, A Heather

AU - Fournier, Agnes

AU - Garcia-Closas, Montse

AU - Giles, Graham

AU - Guevara, Marcela

AU - Hankinson, Susan E

AU - Heath, Alicia

AU - Jones, Michael E

AU - Joshu, Corinne E

AU - Kaaks, Rudolf

AU - Kirsh, Victoria A

AU - Kitahara, Cari M

AU - Koh, Woon-Puay

AU - Linet, Martha S

AU - Park, Hannah Lui

AU - Masala, Giovanna

AU - Mellemkjaer, Lene

AU - Milne, Roger L

AU - O'Brien, Katie M

AU - Palmer, Julie R

AU - Riboli, Elio

AU - Rohan, Thomas E

AU - Shrubsole, Martha J

AU - Sund, Malin

AU - Tamimi, Rulla

AU - Tin Tin, Sandar

AU - Visvanathan, Kala

AU - Vermeulen, Roel Ch

AU - Weiderpass, Elisabete

AU - Willett, Walter C

AU - Yuan, Jian-Min

AU - Zeleniuch-Jacquotte, Anne

AU - Nichols, Hazel B

AU - Sandler, Dale P

AU - Swerdlow, Anthony J

AU - Schoemaker, Minouk J

AU - Weinberg, Clarice R

PY - 2024/4

Y1 - 2024/4

N2 - BACKGROUND: A high body mass index (BMI, kg/m 2) 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.

AB - BACKGROUND: A high body mass index (BMI, kg/m 2) 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.

UR - https://www.scopus.com/pages/publications/85185593933

U2 - 10.1016/j.canep.2024.102545

DO - 10.1016/j.canep.2024.102545

M3 - Article

C2 - 38377945

SN - 1877-7821

VL - 89

JO - Cancer Epidemiology

JF - Cancer Epidemiology

M1 - 102545

ER -

BMI and breast cancer risk around age at menopause

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