{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:03:07Z","timestamp":1789380187718,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      Advanced breast cancer is a leading cause of cancer\u2010associated death in women. It is critical to find biomarkers to identify patients who are more prone to progress to advanced disease and would be better served with more aggressive treatments. Hormone receptor\u2010positive breast cancers make up about 70% of all breast cancers. The analysis of gene amplification and expression has been utilized to classify breast tumors into medically useful risk groups. In the present study, we selected five genes (\n                      <jats:italic>MMP11<\/jats:italic>\n                      ,\n                      <jats:italic>CTSV<\/jats:italic>\n                      ,\n                      <jats:italic>CD68<\/jats:italic>\n                      ,\n                      <jats:italic>SCUBE2<\/jats:italic>\n                      , and\n                      <jats:italic>MYBL2<\/jats:italic>\n                      ) that are important in tumor invasion and metastasis to identify a pattern associated with well\u2010established pathology markers indicative of poor prognosis in early\u2010stage hormone receptor\u2010positive breast cancers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two hundred and thirty\u2010nine early\u2010stage hormone receptor\u2010positive breast cancer patients were analyzed. Patients were required to have FFPE (formalin\u2010fixed paraffin\u2010embedded) samples from the primary tumor. Expression of the selected genes was determined using TaqMan expression assays.\n                      <jats:italic>MYBL2<\/jats:italic>\n                      amplification was examined using fluorescent in situ hybridization (FISH).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Expression of\n                      <jats:italic>CTSV<\/jats:italic>\n                      was significantly associated with increasing tumor size (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) and lymph node involvement (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016). In multivariate analysis,\n                      <jats:italic>CTSV<\/jats:italic>\n                      expression remained significantly associated with lymph node involvement (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.049). Expression of\n                      <jats:italic>MYBL2<\/jats:italic>\n                      was associated with higher tumor grade (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). We identified\n                      <jats:italic>MYBL2<\/jats:italic>\n                      amplification in one sample. Expression of\n                      <jats:italic>SCUBE2<\/jats:italic>\n                      was inversely associated with tumor grade (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04). Receiver\u2010operator characteristic (ROC) analysis was used to predict lymph node involvement using clinicopathologic features (age at diagnosis, tumor size, and histologic grade), and the five gene expression markers, which resulted in AUC\u2009=\u20090.83.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We found a significant association between\n                      <jats:italic>CTSV<\/jats:italic>\n                      ,\n                      <jats:italic>MYBL2<\/jats:italic>\n                      , and\n                      <jats:italic>SCUBE2<\/jats:italic>\n                      expression and pathological variables of poor prognosis. Our study reveals that analysis of the expression of these genes may help identify early\u2010stage hormone receptor\u2010positive breast tumors that are more likely to metastasize and need more intense treatment modalities.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.72780","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:06:51Z","timestamp":1783404411000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Significance of Tumor Invasion Gene Profiling in Early\u2010Stage Hormone Receptor\u2010Positive Breast Cancer: A Cross\u2010Sectional Study"],"prefix":"10.1002","volume":"9","author":[{"given":"Shayan","family":"Forghani","sequence":"first","affiliation":[{"name":"Cancer Research Center Shahid Beheshti University of Medical Sciences Tehran 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