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Adv."],"published-print":{"date-parts":[[2026,9,25]]},"abstract":"<jats:p>\n                    Male breast cancer (MBC) is rare and remains largely managed using knowledge derived from female breast cancer. Here, we generated a multiplatform single-cell and spatial transcriptomic atlas integrating scRNA-seq, SeekSpace, Visium HD, Xenium In Situ, and multiplex immunohistochemistry data from male and female breast cancer cohorts, covering more than 660,000 cells. We identified male-specific tumor cells (MSTCs) that were enriched in MBC, rare in female breast cancer, and associated with poorer disease-free survival. MSTCs exhibited neural transcriptional programs, increased transcriptome-inferred copy number variation burden, and spatial coupling with fatty acid metabolism signals. MSTC-enriched regions showed reduced antigen-presentation signatures and spatial association with\n                    <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic toggle=\"yes\">\/CD163<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    macrophages, with\n                    <jats:italic toggle=\"yes\">GRN-SORT1<\/jats:italic>\n                    emerging as a candidate macrophage-tumor interaction axis. These findings define an MBC-associated malignant state and its immune-metabolic spatial context.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeg7722","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:58:53Z","timestamp":1790359133000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Multiplatform single-cell and spatial transcriptomics reveal sex-specific malignant states and architecture in male breast cancer"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6028-0185","authenticated-orcid":true,"given":"Haoyuan","family":"Shi","sequence":"first","affiliation":[{"name":"School of Future Medicine, Beijing University of Chinese Medicine, Beijing 100102, China."},{"name":"Department of Urology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China."},{"name":"State Key Laboratory of Molecular Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5694-0101","authenticated-orcid":true,"given":"Xiuli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Peking University First Hospital, Beijing 100034, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1566-6215","authenticated-orcid":true,"given":"Shouliang","family":"Cai","sequence":"additional","affiliation":[{"name":"The Ansteel Group Hospital, Anshan 114001, Liaoning, 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