{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:07:16Z","timestamp":1780337236712,"version":"3.54.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Breast cancer remains a global public health challenge. This study aimed to investigate the relationships between serum levels of insulin-like growth factor binding protein 3 (IGFBP-3), insulin-like growth factor 1 (IGF-1), the IGFBP-3 A-202C polymorphism and hormone receptor subtypes: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) with respect to breast cancer risk in Palestinian women. A cross-sectional study was conducted on 112 newly diagnosed, histopathologically confirmed breast cancer patients. Data collection included structured interviews and laboratory analyses, including biochemical, genetic, and immunohistochemical assessments. The tumor tissue samples were analyzed for ER, PR, and HER-2 status. SPSS version 28 was used for all data analysis. A high prevalence of hormone receptor positivity was observed. Among the breast cancer patients, 87.5% were ER positive and 84.8% were PR positive. A total of 75.9% were HER-2 negative. The IGFBP-3 A-202C genotype is significantly associated with PR and combined ER\/PR positivity (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.020). Patients with ER(+)\/PR(+) status had significantly higher serum IGF-1 and IGFBP-3 levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.001), with IGF-1 levels positively correlated with hormone receptor status (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>s<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u20090.232,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.001) and advanced disease stages, moderately with Stage III (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>s<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u20090.191,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.001) and weakly correlated with Stage IV (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>s<\/jats:italic>\n                    <\/jats:sub>\n                    \u2009=\u20090.119,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.029). These findings suggest that IGF-1 and IGFBP-3 may have potential as candidate biomarkers for breast cancer risk and progression. Integrating genetic, biochemical, and hormone receptor status provides novel insights into breast cancer biology and may support future research on personalized prevention and treatment strategies, particularly in resource-limited settings such as the Gaza Strip.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0350553","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:31:07Z","timestamp":1780335067000},"page":"e0350553","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interplay of the IGFBP-3 polymorphism and serum levels of IGF-1\/IGFBP-3 with hormone receptor subtypes in patients with breast cancer among Palestinian women"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2710-5673","authenticated-orcid":true,"given":"Heba Mohammed","family":"Arafat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-1679","authenticated-orcid":true,"given":"Tengku Ahmad Damitri Al-Astani","family":"Tengku Din","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3959-4534","authenticated-orcid":true,"given":"Noorazliyana","family":"Shafii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8393-7899","authenticated-orcid":true,"given":"Rosediani","family":"Muhamad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihab","family":"Naser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahed","family":"Al Laham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohood Mohammed","family":"Shamallakh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"pone.0350553.ref001","unstructured":"World Health Organization. Breast cancer. 2024 [cited 2025 22 May]. Available from: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/breast-cancer"},{"key":"pone.0350553.ref002","author":"JEM Ferlay","year":"2024"},{"key":"pone.0350553.ref003","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1002\/cncr.32887","article-title":"Breast cancer early detection: A phased approach to implementation","volume":"126","author":"O Ginsburg","year":"2020","journal-title":"Cancer"},{"key":"pone.0350553.ref004","unstructured":"Ministry of Health. Health Annual Report Palestine 2022. Ministry of Health: Palestinian Health Information Center (PHIC), Health Policy & Planning Unit, Ministry of Health. 2023."},{"key":"pone.0350553.ref005","unstructured":"Ministry of Health. Palestine Health Status Annual Report, 2018. 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Satpathi","year":"2023","journal-title":"Cureus"},{"issue":"5","key":"pone.0350553.ref009","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1210\/endrev\/bnad008","article-title":"Signaling Pathways of the Insulin-like Growth Factor Binding Proteins","volume":"44","author":"RC Baxter","year":"2023","journal-title":"Endocr Rev"},{"issue":"17","key":"pone.0350553.ref010","doi-asserted-by":"crossref","first-page":"9302","DOI":"10.3390\/ijms25179302","article-title":"Decoding the Role of Insulin-like Growth Factor 1 and Its Isoforms in Breast Cancer","volume":"25","author":"A Kotsifaki","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0350553.ref011","doi-asserted-by":"crossref","first-page":"113862","DOI":"10.1016\/j.yexcr.2023.113862","article-title":"Insulin promotes growth in breast cancer cells through the type I IGF receptor in insulin receptor deficient cells","volume":"434","author":"M Monteiro","year":"2024","journal-title":"Exp Cell 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Concordance between Immuno-Histochemistry and MapQuant\u2122 Microarray Based Assay","volume":"11","author":"D Mouttet","year":"2016","journal-title":"PLoS One"},{"key":"pone.0350553.ref032","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ghir.2017.02.001","article-title":"Serum IGF-1, IGFBP-3 levels and circulating tumor cells (CTCs) in early breast cancer patients","volume":"33","author":"GZ Papadakis","year":"2017","journal-title":"Growth Horm IGF Res"},{"key":"pone.0350553.ref033","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.biopha.2015.02.018","article-title":"Impact of the IGFBP3 A-202C polymorphism on susceptibility and clinicopathologic features of breast cancer","volume":"71","author":"X Ma","year":"2015","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"pone.0350553.ref034","doi-asserted-by":"crossref","first-page":"13551","DOI":"10.1038\/s41598-023-40443-8","article-title":"Risk factors for the development of triple-negative breast cancer versus non-triple-negative breast cancer: a case-control study","volume":"13","author":"S Nag","year":"2023","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0350553.ref035","doi-asserted-by":"crossref","DOI":"10.1186\/bcr3462","article-title":"Estrogen receptor negative\/progesterone receptor positive breast cancer is not a reproducible subtype","volume":"15","author":"MM Hefti","year":"2013","journal-title":"Breast Cancer Res"},{"issue":"11","key":"pone.0350553.ref036","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1002\/ijc.28589","article-title":"Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status-A prospective study within the EPIC cohort","volume":"134","author":"R Kaaks","year":"2014","journal-title":"Int J Cancer"},{"issue":"4","key":"pone.0350553.ref037","doi-asserted-by":"crossref","DOI":"10.3747\/co.20.1380","article-title":"Serum insulin-like growth factor 1 correlates with the risk of nodal metastasis in endocrine-positive breast cancer","volume":"20","author":"F Morgillo","year":"2013","journal-title":"Curr Oncol"},{"issue":"10","key":"pone.0350553.ref038","first-page":"619","article-title":"Breast cancer: Role of IGF-1 and IGFBP-3 expression in prognostication","volume":"54","author":"A Raval","year":"2016","journal-title":"Indian J Exp Biol"},{"issue":"4","key":"pone.0350553.ref039","first-page":"435","article-title":"Relationships Between Serum Expression of IGF-1 and Metabolic Syndrome Metrics in Syrian Women with Breast Cancer","volume":"26","author":"H Khaddour","year":"2019","journal-title":"Rom J Diabetes Nutr Metab Dis"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0350553","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:31:15Z","timestamp":1780335075000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0350553"}},"subtitle":[],"editor":[{"given":"Steven A.","family":"Rosenzweig","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0350553","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,1]]}}}