Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies
Open accessAbstract
BACKGROUND: Associations between circulating concentrations of oestrogens, progesterone, and androgens with breast cancer and related risk factors in premenopausal women are not well understood. We aimed to characterise these associations with a pooled analysis of data from seven studies. METHODS: Individual participant data for prediagnostic sex hormone and sex hormone-binding globulin (SHBG) concentrations were contributed from seven prospective studies. We restricted analyses to women who were premenopausal and younger than 50 years at blood collection, and to women with breast cancer diagnosed before age 50 years. We estimated odds ratios (ORs) with 95% CIs for breast cancer associated with hormone concentrations by conditional logistic regression in cases and controls matched for age, date of blood collection, and day of cycle, with stratification by study and further adjustment for cycle phase. We examined associations of hormones with risk factors for breast cancer in control women by comparing geometric mean hormone concentrations in categories of these risk factors, adjusted for study, age, phase of menstrual cycle, and body-mass index (BMI). All statistical tests were two-sided. FINDINGS: We included data for up to 767 women with breast cancer and 1699 controls in the risk analyses. Breast cancer risk was associated with a doubling in concentrations of oestradiol (OR 1·19, 95% CI 1·06-1·35), calculated free oestradiol (1·17, 1·03-1·33), oestrone (1·27, 1·05-1·54), androstenedione (1·30, 1·10-1·55), dehydroepiandrosterone sulphate (1·17, 1·04-1·32), testosterone (1·18, 1·03-1·35), and calculated free testosterone (1·08, 0·97-1·21). Breast cancer risk was not associated with luteal phase progesterone (doubling in concentration OR 1·00, 95% CI 0·92-1·09), and adjustment for other factors had little effect on any of these ORs. Cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors. INTERPRETATION: Circulating oestrogens and androgens are positively associated with the risk for breast cancer in premenopausal women.
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Circulating estrogens are associated with increased breast cancer risk in women, and this cancer is related to alcohol intake.
“Because circulating estrogens are associated to an increased breast cancer risk in women, [123][124][125] and this cancer is related to alcohol intake, 126,127”
From The chronic alcohol consumption influences the gonadal axis in men: Results from a meta‐analysis (2024) · cites this paper as [123]
Alcohol may affect serum levels of hormones and related signalling pathways, leading to an increased risk of breast cancer, and possibly of prostate, ovarian and endometrial cancers.
“Secondly, alcohol may affect serum levels of hormones and related signalling pathways, leading to an increased risk of breast cancer, and possibly of prostate, ovarian and endometrial cancers 153, 154, 155.”
From The relationship between different dimensions of alcohol use and the burden of disease—an update (2017) · cites this paper as [154]
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- Authors
- †
- Corresponding author
- †
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 14
- Issue
- 10
- Pages
- 1009-1019
- ISSN
- 1470-2045 (ISSN-L)
- PMC
- PMC4056766
- OpenAlex
- W157836986
- Cited by
- 399
- References
- 42
- Citations by year
- 2026: 27 · 2025: 39 · 2024: 34 · 2023: 32 · 2022: 38 · 2021: 38 · 2020: 38 · 2019: 22 · 2018: 24 · 2017: 22 · 2016: 23 · 2015: 33 · 2014: 27 · 2013: 2
- FWCI
- 15.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Lancet Oncology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Funders
- National Institute for Health and Care Research (NF-SI-0512-10122)
- National Cancer Institute (R01CA050385, R01CA067262)
- 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
- premenopausal women, sex hormones, estradiol, estrone, androgens, testosterone, dehydroepiandrosterone sulfate, androstenedione, progesterone, sex hormone-binding globulin, menstrual cycle phases, breast cancer risk factors, body mass index
- MeSH terms
- Adult, Breast Neoplasms, Cooperative Behavior, Female, Humans, Prospective Studies, Sex Hormone-Binding Globulin, Gonadal Steroid Hormones, Body Mass Index, Premenopause, Dehydroepiandrosterone Sulfate
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