{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:56:30Z","timestamp":1790146590222,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T00:00:00Z","timestamp":1561507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001026","name":"National Breast Cancer Foundation","doi-asserted-by":"publisher","award":["ECF\u201015\u2010012"],"award-info":[{"award-number":["ECF\u201015\u2010012"]}],"id":[{"id":"10.13039\/501100001026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1104975"],"award-info":[{"award-number":["1104975"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1150591"],"award-info":[{"award-number":["1150591"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["209057"],"award-info":[{"award-number":["209057"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["396414"],"award-info":[{"award-number":["396414"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["504711"],"award-info":[{"award-number":["504711"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005921","name":"International Arctic Research Center, University of Alaska, Fairbanks","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000951","name":"Cancer Council Victoria","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000951","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,3,15]]},"abstract":"<jats:p>\n                    Adiposity increases estrogen receptor (ER)\u2010positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex\u2010steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER\u2010positive postmenopausal breast cancer association. We used data from a case\u2013cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER\u2010negative disease or breast cancer diagnosis within the first follow\u2010up year were excluded. We analyzed the study as a cumulative sampling case\u2013control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression\u2010based multiple\u2010mediator approach. For women with body mass index (BMI) &gt;30\u2009kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    compared to women with BMI 18.5\u201325\u2009kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    , the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05\u20132.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43\u20132.48). Percentage mediated effect through free estradiol was 72% (IIE\u2010RR 1.56; 95% CI 1.11\u20132.19). There was no evidence for an indirect effect through insulin (IIE\u2010RR 1.12; 95% CI 0.68\u20131.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity\u2013breast cancer relationship but does not explain all of the association.\n                  <\/jats:p>","DOI":"10.1002\/ijc.32504","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T03:39:36Z","timestamp":1560310776000},"page":"1541-1552","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Adiposity and estrogen receptor\u2010positive, postmenopausal breast cancer risk: Quantification of the mediating effects of fasting insulin and free estradiol"],"prefix":"10.1002","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-7220","authenticated-orcid":false,"given":"S. Ghazaleh","family":"Dashti","sequence":"first","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health The University of Melbourne  Melbourne VIC Australia"},{"name":"Cancer Epidemiology and Intelligence Division Cancer Council Victoria  Melbourne VIC Australia"},{"name":"Section of Nutrition and Metabolism International Agency for Research on Cancer (IARC)  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health The University of Melbourne  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Karahalios","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health The University of Melbourne  Melbourne VIC 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Health The University of Melbourne  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"MacInnis","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health The University of Melbourne  Melbourne VIC Australia"},{"name":"Cancer Epidemiology and Intelligence Division Cancer Council Victoria  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigid M.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health The University of Melbourne  Melbourne VIC Australia"},{"name":"Cancer Epidemiology and Intelligence Division Cancer Council Victoria  Melbourne VIC Australia"},{"name":"Physical Activity Laboratory Baker Heart and Diabetes Institute  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Baglietto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard A.","family":"Morris","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences University of South Australia  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc J.","family":"Gunter","sequence":"additional","affiliation":[{"name":"Section of Nutrition and Metabolism International Agency for Research on Cancer (IARC)  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Section of Nutrition and Metabolism International Agency for Research on Cancer (IARC)  Lyon 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