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However, the mechanisms of invasion are still largely unknown. At the DCIS stage, there is an over-representation of HER2-positive lesions compared with invasive breast cancer. In this study, we investigated the associations between gene expression profiles in cancer cells and the immune microenvironment of HER2-positive DCIS and invasive breast tumors with concurrent DCIS using spatial transcriptomics. We found distinctly more B cells in the vicinity of DCIS ducts than in invasive tumor areas. There was higher expression of genes involved in energy metabolism in DCIS cancer cells than in invasive cancer cells and a positive correlation between expression of metabolic genes and B-cell abundance in DCIS. In contrast were processes related to epithelial to mesenchymal transition negatively correlated with B-cell abundance in DCIS. We also found significant correlation between expression of the B-cell-attracting chemokines CCL19, CCL21 and CXCL13 in stromal cells and B cell abundance in DCIS. This study indicates that B cells may play a protective role in the progression of HER2-positive DCIS to invasive breast cancer and that increased metabolic activity in intraductal cancer cells in combination with chemokines produced by stromal cells may influence the immune microenvironment of DCIS. These findings have implications for understanding HER2-positive breast cancer progression.<\/jats:p>","DOI":"10.1186\/s13058-025-01990-2","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T15:26:53Z","timestamp":1742570813000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["B cells and energy metabolism in HER2-positive DCIS: insights into breast cancer progression from spatial-omics analyses"],"prefix":"10.1186","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-1106","authenticated-orcid":false,"given":"Helga","family":"Bergholtz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2689-7154","authenticated-orcid":false,"given":"Jens Henrik","family":"Norum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonje Gulbrandsen","family":"Lien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina Landschoof","family":"Skrede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8ystein","family":"Garred","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5995-2319","authenticated-orcid":false,"given":"Therese","family":"S\u00f8rlie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"1990_CR1","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1093\/jncimonographs\/lgq035","volume":"2010","author":"DC Allred","year":"2010","unstructured":"Allred DC. 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Breast Cancer Res. 2018;20:25.","journal-title":"Breast Cancer Res"}],"container-title":["Breast Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13058-025-01990-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13058-025-01990-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13058-025-01990-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:03:29Z","timestamp":1742774609000},"score":1,"resource":{"primary":{"URL":"https:\/\/breast-cancer-research.biomedcentral.com\/articles\/10.1186\/s13058-025-01990-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1990"],"URL":"https:\/\/doi.org\/10.1186\/s13058-025-01990-2","relation":{},"ISSN":["1465-542X"],"issn-type":[{"value":"1465-542X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,21]]},"assertion":[{"value":"22 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was conducted in compliance with the principles of the Declaration of Helsinki. Ethics approval was given by each institution\u2019s internal review and ethics board (approval numbers: 2016\/433 and 2019\/657 (Oslo, Norway), PG\/U-25\/01\/2012-00001497 (Milan, Italy)). All patients have given written consent for the use of tumor tissue for research purposes.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics declarations and consent to participate"}},{"value":"Not applicable as no identifiable patient information is disclosed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The single cell spatial protein analyses were funded by NanoString as a grant to Helga Bergholtz (CosMx Protein Grant).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"44"}}