Genomic characterization of the HER2-enriched intrinsic molecular subtype in primary ER-positive HER2-negative breast cancer
(2025) In Nature Communications 16. p.1-17- 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... (More)
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.
(Less)
- author
- organization
-
- Research Group Lung Cancer (research group)
- Breast/lung cancer (research group)
- LUCC: Lund University Cancer Centre
- Division of Translational Cancer Research
- Molecular therapeutics in breast cancer (research group)
- Breast and Ovarian Cancer Genomics (research group)
- Systems Immunology (research group)
- Breastcancer-genetics
- Familial Breast Cancer (research group)
- publishing date
- 2025
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 16
- article number
- 2208
- pages
- 1 - 17
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:40044693
- scopus:86000563682
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-025-57419-z
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s) 2025.
- id
- d40087c1-dd94-4dce-9689-88344f750146
- date added to LUP
- 2025-04-01 23:06:59
- date last changed
- 2025-07-23 07:49:47
@article{d40087c1-dd94-4dce-9689-88344f750146, abstract = {{<p>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.</p>}}, author = {{Hohmann, Lennart and Sigurjonsdottir, Kristin and Campos, Ana Bosch and Nacer, Deborah F. and Veerla, Srinivas and Rosengren, Frida and Reddy, Poojaswini Thimmaraya and Häkkinen, Jari and Nordborg, Nicklas and Vallon-Christersson, Johan and Memari, Yasin and Black, Daniella and Bowden, Ramsay and Davies, Helen R. and Borg, Åke and Nik-Zainal, Serena and Staaf, Johan}}, issn = {{2041-1723}}, language = {{eng}}, pages = {{1--17}}, publisher = {{Nature Publishing Group}}, series = {{Nature Communications}}, title = {{Genomic characterization of the HER2-enriched intrinsic molecular subtype in primary ER-positive HER2-negative breast cancer}}, url = {{http://dx.doi.org/10.1038/s41467-025-57419-z}}, doi = {{10.1038/s41467-025-57419-z}}, volume = {{16}}, year = {{2025}}, }