Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies
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Abstract
BACKGROUND: Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. METHODS: Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. FINDINGS: Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons). INTERPRETATION: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours. FUNDING: Cancer Research UK.
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The record
- Venue
- The Lancet Oncology
- Topic
- Cancer Risks and Factors
- Field
- Medicine
- Canadian institutions
- —
- Funders
- National Institute of Child Health and Human DevelopmentNational Cancer InstituteNorwegian Institute of Public HealthUniversity of California, San FranciscoUniversity of North Carolina at Chapel HillInstituto Nacional De Salud PúblicaInstitut Gustave-RoussyWuhan UniversitySyddansk UniversitetUniversidad de Costa RicaUniversitetet i BergenOdense UniversitetshospitalMemorial Sloan-Kettering Cancer CenterUniversità degli Studi di PadovaUniversiteit MaastrichtImperial College LondonWorld Health OrganizationUniversity of Southern CaliforniaUniversity College LondonCancer Research UKLondon School of Hygiene and Tropical MedicineLoma Linda UniversityUniversity of OtagoShanghai Institute Of Planned Parenthood ResearchDeutsches KrebsforschungszentrumUniversity of PittsburghNational and Kapodistrian University of AthensKarolinska InstitutetUniversidad de ChileInstitut National de la Santé et de la Recherche MédicaleUniversity of MinnesotaUniversità degli Studi di MilanoUniversity of PennsylvaniaVanderbilt UniversityUniversity of TorontoNational University of SingaporeKaiser Permanente
- Keywords
- MenarcheBreast cancerEpidemiologyMenopauseMedicineObstetricsGynecologyCancerDemographyInternal medicineSociology
- Has abstract in OpenAlex
- yes