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The objective of this analysis was to investigate whether tumor-specific RANK and RANKL expression in patients with primary breast cancer is associated with high percentage mammographic density (PMD), which is a known breast cancer risk factor.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Immunohistochemical staining of RANK and RANKL was performed in tissue microarrays (TMAs) from primary breast cancer samples of the Bavarian Breast Cancer Cases and Controls (BBCC) study. For RANK and RANKL expression, histochemical scores (H scores) with a cut-off value of\u2009&gt;\u20090 vs 0 were established. PMD was measured in the contralateral, non-diseased breast. Linear regression models with PMD as outcome were calculated using common predictors of PMD (age at breast cancer diagnosis, body mass index (BMI) and parity) and RANK and RANKL H scores. Additionally, Spearman rank correlations (\u03c1) between PMD and RANK and RANKL H score were performed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In the final cohort of 412\u00a0patients, breast cancer-specific RANK and RANKL expression was not associated with PMD (<jats:italic>P<\/jats:italic>\u2009=\u20090.68). There was no correlation between PMD and RANK H score (Spearman\u2019s\u00a0\u03c1\u2009=\u20090.01, <jats:italic>P<\/jats:italic>\u2009=\u20090.87) or RANKL H score (Spearman\u2019s\u00a0\u03c1\u2009=\u20090.04, <jats:italic>P<\/jats:italic>\u2009=\u20090.41). RANK expression was highest in triple-negative tumors, followed by HER2-positive, luminal B-like and luminal A-like tumors, while no subtype-specific expression of RANKL was found.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Results do not provide evidence for an association of RANK and RANKL expression in primary breast cancer with PMD.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00404-024-07495-1","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T12:15:55Z","timestamp":1717589755000},"page":"1223-1233","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Correlation of RANK and RANKL with mammographic density in primary breast cancer patients"],"prefix":"10.1007","volume":"310","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7280-7697","authenticated-orcid":false,"given":"Marius","family":"Wunderle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Heindl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika S.","family":"Behrens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lothar","family":"H\u00e4berle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolin C.","family":"Hack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Heusinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Huebner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Gass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Ruebner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00fcdiger","family":"Schulz-Wendtland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramona","family":"Erber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arndt","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias W.","family":"Beckmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William C.","family":"Dougall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael F.","family":"Press","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4885-8471","authenticated-orcid":false,"given":"Peter A.","family":"Fasching","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julius","family":"Emons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"issue":"8","key":"7495_CR1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1055\/s-0032-1315129","volume":"72","author":"C Rauh","year":"2012","unstructured":"Rauh C, Hack CC, Haberle L et al (2012) Percent mammographic density and dense area as risk factors for breast cancer. 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The institution of <b>AH<\/b> and <b>RE<\/b> conducts research for AstraZeneca, Biocartis, BioNTech, Cepheid, Gilead, Janssen-Cilag, Mindpeak, MSD, NanoString Technologies, Novartis, palleos healthcare, Owkin, Roche, and ZytoVision. <b>CCH<\/b> has received honoraria from AstraZeneca, Daiichi Sankyo, Eisai, Gilead, MSD, Novartis, Pfizer, and Roche. <b>JE<\/b> has received honoraria from Eisai, Novartis, and Pfizer. <b>PAF<\/b> has received honoraria from Agendia, AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Gilead, Hexal, Lilly, MacroGenics, Merck Sharp and Dohme, Novartis, Pfizer, Pierre Fabre, Roche, Seattle Genetics, and received grant support from BioNTech and Cepheid. <b>PG<\/b> has received honoraria from AstraZeneca, MSD, and Novartis. <b>MFP<\/b> has received consulting fees from AstraZeneca, Curio Science, Eli Lilly & Company, Lilly USA, LLC, Merck & Co, Novartis Pharmaceuticals Corporation, and Zymeworks Inc, honoraria for speaking engagements from Physicians\u2019 Education Resource\u00ae, LLC (PER\u00ae) and Medscape, and he reports institutional support from TORL BioTherapeutics LLC. <b>WCD<\/b> is a member of the EpimAb Biotherapeutics scientific advisory board and holds patents related to the Receptor Activator of Nuclear Factor-\u03ba B Ligand (RANKL) pathway. The other authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was approved by the ethics committee of the Faculty of Medicine at\u00a0Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (reference numbers 2700 and 297_17\u00a0BC). All procedures performed in this study were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}]}}