{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T11:28:31Z","timestamp":1793705311452,"version":"4.5.1"},"reference-count":56,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031478","name":"Next Generation EU","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PNRR M6C2"},{"name":"Investimento 2.1 Valorizzazione e potenziamento della ricerca biomedica del SSN","award":["PNRR-MAD-2022"],"award-info":[{"award-number":["PNRR-MAD-2022"]}]},{"name":"Investimento 2.1 Valorizzazione e potenziamento della ricerca biomedica del SSN","award":["12376567"],"award-info":[{"award-number":["12376567"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Low levels of sex hormone\u2013binding globulin (SHBG) have been associated with increased breast cancer (BC) risk, particularly in postmenopausal women. Whether this association extends to premenopausal women remains uncertain. We therefore performed an individual-patient pooled analysis and a meta-analysis to evaluate SHBG\u2019s role as a biomarker across menopausal status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The pooled analysis included women at increased BC risk enrolled in 2 low-dose tamoxifen trials. The meta-analysis included 11 independent published studies assessing the association of SHBG with BC risk in healthy premenopausal women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among premenopausal women in the pooled high-risk cohort, SHBG levels above the lowest tertile were associated with a 40% lower hazard of subsequent BC events (hazard ratio [HR] = 0.60; 95% confidence interval [CI] = 0.38 to 0.96; P\u2009=\u2009.03). In the meta-analysis, comprising 35\u2009167 premenopausal women and 2302 BC events, the summary estimate in premenopausal women showed a nonsignificant 8% risk reduction (Summary Odds Ratio [SOR] = 0.92; 95% CI = 0.78 to 1.09). On the other hand, among the 7 studies reporting stratified data by menopausal status, postmenopausal women experienced a significant 23% risk reduction (SOR = 0.77; 95% CI = 0.69 to 0.87), with no statistically significant heterogeneity by menopausal status (P\u2009=\u2009.28).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In a selected high-risk population, higher baseline SHBG was associated with fewer subsequent BC events. However, the meta-analysis did not provide statistically significant evidence of an inverse association with BC occurrence in premenopausal women. These findings suggest that SHBG may be a biomarker of subsequent breast events in high-risk settings but do not confirm its role as a risk biomarker in the general premenopausal population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djag318","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:51:50Z","timestamp":1789127510000},"source":"Crossref","is-referenced-by-count":0,"title":["SHBG as a breast cancer risk biomarker in premenopausal women? Results from an individual patient\u2019s pooled analysis and a meta-analysis"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-4108","authenticated-orcid":false,"given":"Davide","family":"Serrano","sequence":"first","affiliation":[{"name":"Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO) IRCCS , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0059-3372","authenticated-orcid":false,"given":"Roberta","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, European Institute of Oncology (IEO) IRCCS , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4131-2030","authenticated-orcid":false,"given":"Harriet","family":"Johansson","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, European Institute of 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Institute of Oncology (IEO) IRCCS , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2162-4002","authenticated-orcid":false,"given":"Matteo","family":"Lazzeroni","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO) IRCCS , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Aurilio","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO) IRCCS , Milan,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9907-3299","authenticated-orcid":false,"given":"Alessio","family":"Carbone","sequence":"additional","affiliation":[{"name":"Division Medical Oncology, Galliera Hospital , 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