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

Premenopausal Breast Cancer Collaborative Group

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e181771
JournalJAMA oncology
Volume4
Issue number11
DOIs
StatePublished - Nov 1 2018

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Body Mass Index
Breast Neoplasms
Hormones
Progesterone Receptors
Estrogen Receptors
Neoplasms
Age Factors
Adiposity
Risk Reduction Behavior
Menopause
Causality
Epidemiology
Age Groups
Regression Analysis
Outcome Assessment (Health Care)
Weights and Measures

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women. / Premenopausal Breast Cancer Collaborative Group.

In: JAMA oncology, Vol. 4, No. 11, 01.11.2018, p. e181771.

Research output: Contribution to journalArticle

Premenopausal Breast Cancer Collaborative Group. / Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women. In: JAMA oncology. 2018 ; Vol. 4, No. 11. pp. e181771.
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title = "Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women",
abstract = "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.",
author = "{Premenopausal Breast Cancer Collaborative Group} and Schoemaker, {Minouk J.} and Nichols, {Hazel B.} and Wright, {Lauren B.} and Brook, {Mark N.} and Jones, {Michael E.} and O'Brien, {Katie M.} and Adami, {Hans Olov} and Laura Baglietto and Leslie Bernstein and Bertrand, {Kimberly A.} and Boutron-Ruault, {Marie Christine} and Tonje Braaten and Yu Chen and Connor, {Avonne E.} and Miren Dorronsoro and Laure Dossus and Eliassen, {A. Heather} and Giles, {Graham G.} and Hankinson, {Susan E.} and Rudolf Kaaks and Key, {Timothy J.} and Kirsh, {Victoria A.} and Kitahara, {Cari M.} and Koh, {Woon Puay} and Larsson, {Susanna C.} and Linet, {Martha S.} and Huiyan Ma and Giovanna Masala and Merritt, {Melissa A.} and Milne, {Roger L.} and Kim Overvad and Kotaro Ozasa and Palmer, {Julie R.} and Peeters, {Petra H.} and Elio Riboli and Rohan, {Thomas E.} and Atsuko Sadakane and Malin Sund and Tamimi, {Rulla M.} and Antonia Trichopoulou and Giske Ursin and Lars Vatten and Kala Visvanathan and Elisabete Weiderpass and Willett, {Walter C.} and Alicja Wolk and Yuan, {Jian Min} and Anne Zeleniuch-Jacquotte and Sandler, {Dale P.} and Swerdlow, {Anthony J.}",
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month = "11",
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TY - JOUR

T1 - Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women

AU - Premenopausal Breast Cancer Collaborative Group

AU - Schoemaker, Minouk J.

AU - Nichols, Hazel B.

AU - Wright, Lauren B.

AU - Brook, Mark N.

AU - Jones, Michael E.

AU - O'Brien, Katie M.

AU - Adami, Hans Olov

AU - Baglietto, Laura

AU - Bernstein, Leslie

AU - Bertrand, Kimberly A.

AU - Boutron-Ruault, Marie Christine

AU - Braaten, Tonje

AU - Chen, Yu

AU - Connor, Avonne E.

AU - Dorronsoro, Miren

AU - Dossus, Laure

AU - Eliassen, A. Heather

AU - Giles, Graham G.

AU - Hankinson, Susan E.

AU - Kaaks, Rudolf

AU - Key, Timothy J.

AU - Kirsh, Victoria A.

AU - Kitahara, Cari M.

AU - Koh, Woon Puay

AU - Larsson, Susanna C.

AU - Linet, Martha S.

AU - Ma, Huiyan

AU - Masala, Giovanna

AU - Merritt, Melissa A.

AU - Milne, Roger L.

AU - Overvad, Kim

AU - Ozasa, Kotaro

AU - Palmer, Julie R.

AU - Peeters, Petra H.

AU - Riboli, Elio

AU - Rohan, Thomas E.

AU - Sadakane, Atsuko

AU - Sund, Malin

AU - Tamimi, Rulla M.

AU - Trichopoulou, Antonia

AU - Ursin, Giske

AU - Vatten, Lars

AU - Visvanathan, Kala

AU - Weiderpass, Elisabete

AU - Willett, Walter C.

AU - Wolk, Alicja

AU - Yuan, Jian Min

AU - Zeleniuch-Jacquotte, Anne

AU - Sandler, Dale P.

AU - Swerdlow, Anthony J.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - 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.

AB - 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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U2 - 10.1001/jamaoncol.2018.1771

DO - 10.1001/jamaoncol.2018.1771

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JF - JAMA oncology

SN - 2374-2437

IS - 11

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