Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women
Abstract
BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.
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Obesity is associated with higher circulating and white-adipose-tissue-derived E1 levels.
“obesity is associated with higher circulating and WAT-derived E1 levels (64, 135–138)”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [138]
The Results report that serum estrone was significantly higher with increasing BMI in postmenopausal women, supporting the circulating E1 portion. The paper discusses estrogen production in adipose tissue, but does not measure or specifically report higher white-adipose-tissue-derived estrone levels. (LLM, conf=0.86)
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- Authors
- Endogenous Hormones Breast Cancer Collaborative Group
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Endogenous Hormones Breast Cancer Collaborative Group
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-08-19
- Volume
- 95
- Issue
- 16
- Pages
- 1218-1226
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W1551632868
- Cited by
- 1,093
- References
- 28
- Citations by year
- 2026: 15 · 2025: 19 · 2024: 26 · 2023: 27 · 2022: 45 · 2021: 41 · 2020: 48 · 2019: 42 · 2018: 39 · 2017: 56 · 2016: 50 · 2015: 66 · 2014: 63 · 2013: 68 · 2012: 54
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brigham and Women's Hospital
- University of Southern California
- University of Missouri
- University of Connecticut
- Johns Hopkins University
- University of Pittsburgh
- Kagoshima University
- York University
- University of Oxford
- School of Medicine, New York University
- University of California, San Francisco
- University at Buffalo
- National Cancer Institute
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- Topics
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- breast cancer risk, body mass index, obesity, postmenopausal women, serum sex hormones, estradiol, bioavailable estradiol, estrogen, sex hormone-binding globulin, androgens, estrone, estrone sulfate
- MeSH terms
- Aged, Breast Neoplasms, Estradiol, Female, Humans, Middle Aged, Prospective Studies, Risk Factors, Gonadal Steroid Hormones, Body Mass Index, Logistic Models, Case-Control Studies, Postmenopause, Risk Assessment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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