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Perturbation and stability of PAM50 subtyping in population-based primary invasive breast cancer
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- Veerla, Srinivas (author)
- Lund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Bröst- och ovarialcancer,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Research Group Lung Cancer,Lund University Research Groups,Breast and Ovarian Cancer Genomics,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lung cancer,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Sektion I,Institutionen för kliniska vetenskaper, Lund,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund
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- Hohmann, Lennart (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lung cancer,Lund University Research Groups,Forskningsgrupp Lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Research Group Lung Cancer,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund
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- Nacer, Deborah F. (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lung cancer,Lund University Research Groups,Forskningsgrupp Lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Research Group Lung Cancer,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund
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- 2023
- 2023
- English.
- In: npj Breast Cancer. - 2374-4677. ; 9:1
- Journal article (peer-reviewed)
Abstract
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- PAM50 gene expression subtypes represent a cornerstone in the molecular classification of breast cancer and are included in risk prediction models to guide therapy. We aimed to illustrate the impact of included genes and biological processes on subtyping while considering a tumor’s underlying clinical subgroup defined by ER, PR, and HER2 status. To do this we used a population-representative and clinically annotated early-stage breast tumor cohort of 6233 samples profiled by RNA sequencing and applied a perturbation strategy of excluding co-expressed genes (gene sets). We demonstrate how PAM50 nearest-centroid classification depends on biological processes present across, but also within, ER/PR/HER2 subgroups and PAM50 subtypes themselves. Our analysis highlights several key aspects of PAM50 classification. Firstly, we demonstrate the tight connection between a tumor’s nearest and second-nearest PAM50 centroid. Additionally, we show that the second-best subtype is associated with overall survival in ER-positive, HER2-negative, and node-negative disease. We also note that ERBB2 expression has little impact on PAM50 classification in HER2-positive disease regardless of ER status and that the Basal subtype is highly stable in contrast to the Normal subtype. Improved consciousness of the commonly used PAM50 subtyping scheme will aid in our understanding and interpretation of breast tumors that have seemingly conflicting PAM50 classification when compared to clinical biomarkers. Finally, our study adds further support in challenging the common misconception that PAM50 subtypes are distinct classes by illustrating that PAM50 subtypes in tumors represent a continuum with prognostic implications.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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