{"entity": "researcher", "timestamp": "2026-07-10T07:45:07.905Z", "family": "Hohmann", "given": "Lennart", "initials": "L", "orcid": "0000-0002-0281-7140", "affiliations": ["Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.", "Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/b605a3b893a24a238b5bb6eddd27b672.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/b605a3b893a24a238b5bb6eddd27b672"}}, "publications": [{"entity": "publication", "iuid": "b7284178e7704139b443a0f9e1f75614", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b7284178e7704139b443a0f9e1f75614.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b7284178e7704139b443a0f9e1f75614"}}, "title": "Homologous recombination deficiency in primary ER-positive and HER2-negative breast cancer.", "authors": [{"family": "Davies", "given": "Helen R", "initials": "HR", "orcid": "0000-0001-6381-3664", "researcher": {"href": "https://publications.scilifelab.se/researcher/e02b6738c9e140858456e24cef5d6b42.json"}}, {"family": "Black", "given": "Daniella", "initials": "D"}, {"family": "Kvist", "given": "Anders", "initials": "A", "orcid": "0000-0002-1358-0695", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e6b39bdc00c442f94caed782772a278.json"}}, {"family": "Sigurj\u00f3nsd\u00f3ttir", "given": "Krist\u00edn", "initials": "K"}, {"family": "Bosch", "given": "Ana", "initials": "A"}, {"family": "Bowden", "given": "Ramsay", "initials": "R", "orcid": "0000-0003-1138-4452", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b6effa9663145dabd83b3ced199385c.json"}}, {"family": "Memari", "given": "Yasin", "initials": "Y"}, {"family": "Chen", "given": "Ziqian", "initials": "Z"}, {"family": "Rinaldi", "given": "Giuseppe", "initials": "G", "orcid": "0000-0002-5650-6049", "researcher": {"href": "https://publications.scilifelab.se/researcher/da7f30b3dfa5489ba61afa7840bc34c7.json"}}, {"family": "Rosengren", "given": "Frida", "initials": "F"}, {"family": "Nacer", "given": "Deborah F", "initials": "DF", "orcid": "0000-0002-7117-1371", "researcher": {"href": "https://publications.scilifelab.se/researcher/e484e25cfdf64d27842357355409dbfc.json"}}, {"family": "Veerla", "given": "Srinivas", "initials": "S", "orcid": "0000-0001-7328-6239", "researcher": {"href": "https://publications.scilifelab.se/researcher/c203a0b3112f4f499ccc79db3e47b303.json"}}, {"family": "Hohmann", "given": "Lennart", "initials": "L", "orcid": "0000-0002-0281-7140", "researcher": {"href": "https://publications.scilifelab.se/researcher/b605a3b893a24a238b5bb6eddd27b672.json"}}, {"family": "Nordborg", "given": "Nicklas", "initials": "N"}, {"family": "H\u00e4kkinen", "given": "Jari", "initials": "J", "orcid": "0000-0002-8466-9179", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b8605b9a7c74b20986146f020cf4b8f.json"}}, {"family": "Vallon-Christersson", "given": "Johan", "initials": "J", "orcid": "0000-0002-2195-0385", "researcher": {"href": "https://publications.scilifelab.se/researcher/648fa1d04cb640858fe3534d04cd04d1.json"}}, {"family": "Borg", "given": "\u00c5ke", "initials": "\u00c5", "orcid": "0000-0002-5793-132X", "researcher": {"href": "https://publications.scilifelab.se/researcher/127501d4e0854d14a4120acee9042bb7.json"}}, {"family": "Nik-Zainal", "given": "Serena", "initials": "S", "orcid": "0000-0001-5054-1727", "researcher": {"href": "https://publications.scilifelab.se/researcher/af746cf472144e1699ee12fa08921c1d.json"}}, {"family": "Staaf", "given": "Johan", "initials": "J", "orcid": "0000-0001-5254-5115", "researcher": {"href": "https://publications.scilifelab.se/researcher/07acbd7f211e4809a8195e2ccf5faf57.json"}}], "type": "journal article", "published": "2026-02-16", "journal": {"title": "Commun Med (Lond)", "issn": "2730-664X", "volume": "6", "issue": "1", "pages": "118", "issn-l": null}, "abstract": "Homologous recombination deficiency (HRD) originating from inactivation of genes like BRCA1/BRCA2 is a targetable abnormality common in triple-negative breast cancer (TNBC). In estrogen-receptor (ER)-positive HER2-negative (ERpHER2n) breast cancer (BC), HRD prevalence and clinical impact are unclear.\n\nWe analyzed 502 ERpHER2n tumors from patients recruited via the population-representative Swedish SCAN-B study by whole genome sequencing (WGS), defining mutational signatures-based HRD, as well as matched transcriptional, DNA methylation, clinicopathological, adjuvant treatment, and outcome data.\n\nWe show that HRD is much less frequent in ERpHER2n BC (8.4%) compared to TNBC, though induced by similar genetic/epigenetic mechanisms acting on mainly BRCA1/BRCA2/RAD51C/PALB2 together, providing a plausible HR-inactivation mechanism for 71.4% of HRD tumors. Our modelled estimate of HRD in Western European/Nordic BC is ~10-13%. HRD tumors were observed across all PAM50 gene expression subtypes with the exception of Luminal A tumors ( < 1%) and did not exhibit a unique, defining transcriptional or DNA methylation profile. While HRD status was not statistically associated with differences in patient outcome for patients treated with combined chemotherapy and endocrine therapy, a nonsignificant trend of poorer outcome for patients with HRD tumors was observed for patients treated with adjuvant endocrine therapy only.\n\nERpHER2n HRD tumors show features of aggressive disease, but do not display a distinct transcriptional or DNA methylation profile that clearly differentiates them from HR-proficient tumors. Though numbers are limited, we present early evidence that HRD stratification by WGS could impact therapeutic strategies, as HRD BCs trended to poorer outcomes when not treated with chemotherapy.", "doi": "10.1038/s43856-026-01385-0", "pmid": "41699108", "labels": {"NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12909304"}, {"db": "pii", "key": "10.1038/s43856-026-01385-0"}], "notes": [], "created": "2026-06-01T11:12:58.568Z", "modified": "2026-06-01T11:12:58.707Z"}, {"entity": "publication", "iuid": "59ebc9f2f08d46dcafe5fe8d76317dbf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/59ebc9f2f08d46dcafe5fe8d76317dbf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/59ebc9f2f08d46dcafe5fe8d76317dbf"}}, "title": "Genomic characterization of the HER2-enriched intrinsic molecular subtype in primary ER-positive HER2-negative breast cancer.", "authors": [{"family": "Hohmann", "given": "Lennart", "initials": "L", "orcid": "0000-0002-0281-7140", "researcher": {"href": "https://publications.scilifelab.se/researcher/b605a3b893a24a238b5bb6eddd27b672.json"}}, {"family": "Sigurjonsdottir", "given": "Kristin", "initials": "K"}, {"family": "Campos", "given": "Ana Bosch", "initials": "AB"}, {"family": "Nacer", "given": "Deborah F", "initials": "DF", "orcid": "0000-0002-7117-1371", "researcher": {"href": "https://publications.scilifelab.se/researcher/e484e25cfdf64d27842357355409dbfc.json"}}, {"family": "Veerla", "given": "Srinivas", "initials": "S", "orcid": "0000-0001-7328-6239", "researcher": {"href": "https://publications.scilifelab.se/researcher/c203a0b3112f4f499ccc79db3e47b303.json"}}, {"family": "Rosengren", "given": "Frida", "initials": "F"}, {"family": "Reddy", "given": "Poojaswini Thimmaraya", "initials": "PT", "orcid": "0009-0009-7743-4986", "researcher": {"href": "https://publications.scilifelab.se/researcher/868440eeaf364b28aa186eb24b37e2d8.json"}}, {"family": "H\u00e4kkinen", "given": "Jari", "initials": "J", "orcid": "0000-0002-8466-9179", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b8605b9a7c74b20986146f020cf4b8f.json"}}, {"family": "Nordborg", "given": "Nicklas", "initials": "N"}, {"family": "Vallon-Christersson", "given": "Johan", "initials": "J", "orcid": "0000-0002-2195-0385", "researcher": {"href": "https://publications.scilifelab.se/researcher/648fa1d04cb640858fe3534d04cd04d1.json"}}, {"family": "Memari", "given": "Yasin", "initials": "Y"}, {"family": "Black", "given": "Daniella", "initials": "D"}, {"family": "Bowden", "given": "Ramsay", "initials": "R", "orcid": "0000-0003-1138-4452", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b6effa9663145dabd83b3ced199385c.json"}}, {"family": "Davies", "given": "Helen R", "initials": "HR", "orcid": "0000-0001-6381-3664", "researcher": {"href": "https://publications.scilifelab.se/researcher/e02b6738c9e140858456e24cef5d6b42.json"}}, {"family": "Borg", "given": "\u00c5ke", "initials": "\u00c5", "orcid": "0000-0002-5793-132X", "researcher": {"href": "https://publications.scilifelab.se/researcher/127501d4e0854d14a4120acee9042bb7.json"}}, {"family": "Nik-Zainal", "given": "Serena", "initials": "S", "orcid": "0000-0001-5054-1727", "researcher": {"href": "https://publications.scilifelab.se/researcher/af746cf472144e1699ee12fa08921c1d.json"}}, {"family": "Staaf", "given": "Johan", "initials": "J", "orcid": "0000-0001-5254-5115", "researcher": {"href": "https://publications.scilifelab.se/researcher/07acbd7f211e4809a8195e2ccf5faf57.json"}}], "type": "journal article", "published": "2025-03-05", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "2208", "issn-l": "2041-1723"}, "abstract": "ER-positive/HER2-negative (ERpHER2n) breast cancer classified as PAM50 HER2-enriched (ERpHER2n-HER2E) represents a small high-risk patient subgroup. In this study, we investigate genomic, transcriptomic, and clinical features of ERpHER2n-HER2E breast tumors using two primary ERpHER2n cohorts comprising a total of 5640 patients. We show that ERpHER2n-HER2E tumors exhibit aggressive clinical features and poorer clinical outcomes compared to Luminal A and Luminal B tumors. Furthermore, ERpHER2n-HER2E breast cancer does not consist of misclassified or HER2-low cases, has little impact of ERBB2, is highly proliferative and less ER dependent than other luminal subtypes. It is not an obvious biological entity but is nevertheless associated with potentially targetable molecular features, notably a high immune response and high FGFR4 expression. Strikingly, molecular features that define the HER2E subtype in luminal disease are also consistent in HER2-positive disease, including an epigenetic mechanism for high FGFR4 expression in breast cancer.", "doi": "10.1038/s41467-025-57419-z", "pmid": "40044693", "labels": {"NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11882987"}, {"db": "pii", "key": "10.1038/s41467-025-57419-z"}], "notes": [], "created": "2025-09-08T07:15:25.268Z", "modified": "2025-09-08T07:15:25.630Z"}]}