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Tønnes PedersenD. Flesch-JanysN. HakanssonJ. CauleyI. HeuchH. O. AdamiI. PerssonE. WeiderpassC. MagnussonAichi Cancer Center Hospital and Research InstituteAlbert Einstein College of Medicine of Yeshiva UniversityAlberta Health ServicesAmerican Cancer SocietyEmory UniversityIRCCS Centro Di Riferimento Oncologico AvianoMahidol UniversityBank of Cyprus Group Oncology CentreBarts and The London Queen Mary's School of Medicine and DentistryJohns Hopkins UniversityBoston UniversityBritish Columbia Cancer AgencyCalifornia Pacific Medical CenterCancer Council New South WalesInstitute of Oncology, WarsawCancer Prevention Institute of CaliforniaUniversity of Hawaii SystemUniversity of TehranCanadian Cancer Registries Epidemiology Research GroupCancer Research UKClinical Trial Service UnitCatalan Oncology InstituteCenters for Disease Control and PreventionMax Delbruck Center for Molecular MedicineUniversity of MelbourneBrigham and Women's HospitalCancer Institute IndiaChiang Mai UniversityChulalongkorn UniversityColumbia University in the City of New YorkDalla Lana School of Public HealthInstitute of Cancer Epidemiology - DenmarkDanish Nurse Cohort StudyUniversitatsklinikum Hamburg-Eppendorf und Medizinische FakultatKarolinska InstitutetUniversity of PittsburghUniversitetet i BergenGerman Cancer Research CenterUniversity of OtagoNational Cancer Center TokyoFred Hutchinson Cancer Research CenterEpidemiology Unit and Girona Cancer Registry (UERCG)UCLHospital General de MexicoHospital UniversitarioIcelandic Cancer SocietyImperial College LondonInstitut de Cancerologie Gustave RoussyInsermInstituto Nacional de Salud PublicaInternational Agency for Research on CancerInternational Prevention Research InstituteChaim Sheba Medical Center IsraelKaiser PermanenteInstitut Universitaire de Medecine Sociale et Preventive LausanneOnkoloski institut LjubljanaLoma Linda University Adventist Health Sciences CenterLondon School of Hygiene &amp; Tropical MedicineLong Island Breast Cancer StudySkånes universitetssjukhusMaastricht UniversityISPOIcahn School of Medicine at Mount SinaiUniversity of the Philippines ManilaUniversita degli Studi di MilanoFondazione IRCCS Istituto Nazionale dei Tumori, MilanIstituto di Statistica Medica e BiometriaMemorial Sloan-Kettering Cancer CenterNairobi Centre for Research in ReproductionNational Cancer InstituteAustralian National UniversityNational Institute of Child Health and Human DevelopmentNational University of SingaporeThe Netherlands Cancer InstituteNew Jersey State Department of HealthNorwegian Institute of Public HealthDepartment of Public HealthRadiation Effects Research Foundation HiroshimaRoyal College of General Practitioners Oral Contraception StudyRoswell Park Cancer InstituteUniversidad de Costa RicaMedical Center of Fudan UniversityShanghai Institute of Planned Parenthood ResearchCyprus Institute of Neurology and GeneticsWuhan UniversityTianjin Cancer Institute and HospitalTohoku University School of MedicineUniversitetet i TromsoVanderbilt UniversityUniversity Medical Center UtrechtUniversity of Athens Medical SchoolUniversity of California, San FranciscoUniversidad de ChileUniversity of EdinburghUniversity of Minnesota School of Public HealthThe University of North Carolina at Chapel HillUniversity of NottinghamUniversita degli Studi di PadovaUniversity of QueenslandUniversity of Pennsylvania, School of MedicineUniversity of Southern CaliforniaSyddansk UniversitetUniversity of TorontoWomen's Health InitiativeOrganisation Mondiale de la SanteYamagata University Faculty of Medicine2018-06-112018-06-112012-01-01The Lancet Oncology. Vol.13, No.11 (2012), 1141-115114745488147020452-s2.0-84877875905https://repository.li.mahidol.ac.th/handle/20.500.14594/15125Background 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 receptorpositive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.Mahidol UniversityMedicineArticleSCOPUS10.1016/S1470-2045(12)70425-4