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Genomic characterization of the HER2-enriched intrinsic molecular subtype in primary ER-positive HER2-negative breast cancer

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  • معلومة اضافية
    • Contributors:
      Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breast/lungcancer, Research Group Lung Cancer, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröst/lungcancer, Forskningsgrupp Lungcancer, Originator; Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Translational Cancer Research, Breast/lung cancer, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för translationell cancerforskning, Bröst/lungcancer, Originator; Lund University, Profile areas and other strong research environments, Other Strong Research Environments, LUCC: Lund University Cancer Centre, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Övriga starka forskningsmiljöer, LUCC: Lunds universitets cancercentrum, Originator; Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Translational Cancer Research, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för translationell cancerforskning, Originator; Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breastcancer-genetics, Molecular therapeutics in breast cancer, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröstcancer-genetik, Molekylära behandlingsstrategier vid bröstcancer, Originator; Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breast/ovarian cancer, Breast and Ovarian Cancer Genomics, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröst/ovarialcancer, Bröst- och ovarialcancer, Originator; Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Molecular Hematology (DMH), Systems Immunology, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för molekylär hematologi, Systemimmunologi, Originator; Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breastcancer-genetics, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröstcancer-genetik, Originator; Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breastcancer-genetics, Familial Breast Cancer, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröstcancer-genetik, Familjär bröstcancer, Originator
    • نبذة مختصرة :
      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.