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Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series

Vallon-Christersson, Johan, (författare)
Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Section V, Onkologi och Patologi, MV, Oncology and Pathology, MV
Häkkinen, Jari, (författare)
Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Section V, Onkologi och Patologi, MV, Oncology and Pathology, MV
Hegardt, Cecilia, (författare)
Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Section V, Onkologi och Patologi, MV, Oncology and Pathology, MV
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Saal, Lao, (författare)
Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Section V, Onkologi och Patologi, MV, Oncology and Pathology, MV
Larsson, Christer, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för laboratoriemedicin, Department of Laboratory Medicine, Avdelningen för translationell cancerforskning, Division of Translational Cancer Research, Tumörcellsbiologi, Tumor Cell Biology
Ehinger, Anna, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Section V, Onkologi och Patologi, MV, Oncology and Pathology, MV, Individuell Bröstcancerbehandling, Personalized Breast Cancer Treatment
Lindman, H, (författare)
Uppsala University
Olofsson, Helena, (författare)
Uppsala University Hospital
Sjoblom, Tobias (författare)
Wärnberg, Fredrik (författare)
Rydén, Lisa, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Section V, Kirurgi, Lund, Surgery (Lund), Onkologi och Patologi, MV, Oncology and Pathology, MV, Bröstcancerkirurgi, Breast Cancer Surgery, The Liquid Biopsy och Tumörprogression i Bröstcancer, The Liquid Biopsy and Tumor Progression in Breast Cancer
Loman, Niklas, (författare)
Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Section V, Onkologi och Patologi, Kampradlab, Oncology and Pathology, Kamprad Lab, Onkologi och Patologi, MV, Oncology and Pathology, MV, Skåne University Hospital
Malmberg, Martin, (författare)
Skåne University Hospital
Borg, Åke, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Section V, Onkologi och Patologi, MV, Oncology and Pathology, MV, Familjär bröstcancer, Familial Breast Cancer
Staaf, Johan, (författare)
Lunds universitet, Lund University, Medicinska fakulteten, Faculty of Medicine, Institutionen för kliniska vetenskaper, Lund, Department of Clinical Sciences, Lund, Sektion V, Section V, Onkologi och Patologi, MV, Oncology and Pathology, MV
Sjöblom, Tobias, (författare)
Uppsala universitet, Experimentell och klinisk onkologi
Ryden, Lisa, (författare)
Lund Univ, Dept Clin Sci, Div Surg, SE-22185 Lund, Sweden
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet. Medicinska fakulteten. Institutionen för immunologi, genetik och patologi. Experimentell och klinisk onkologi. (creator_code:org_t)
Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet. Medicinska fakulteten. Institutionen för immunologi, genetik och patologi. Klinisk och experimentell patologi. (creator_code:org_t)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet. Medicinska fakulteten. Institutionen för kirurgiska vetenskaper. Endokrinkirurgi. (creator_code:org_t)
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2019
Engelska.
Ingår i: Scientific Reports. - Nature Publishing Group. - 2045-2322. ; 9
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Multigene expression signatures provide a molecular subdivision of early breast cancer associated with patient outcome. A gap remains in the validation of such signatures in clinical treatment groups of patients within population-based cohorts of unselected primary breast cancer representing contemporary disease stages and current treatments. A cohort of 3520 resectable breast cancers with RNA sequencing data included in the population-based SCAN-B initiative (ClinicalTrials.gov ID NCT02306096) were selected from a healthcare background population of 8587 patients diagnosed within the years 2010-2015. RNA profiles were classified according to 19 reported gene signatures including both gene expression subtypes (e.g. PAM50, IC10, CIT) and risk predictors (e.g. Oncotype DX, 70-gene, ROR). Classifications were analyzed in nine adjuvant clinical assessment groups: TNBC-ACT (adjuvant chemotherapy, n = 239), TNBC-untreated (n = 82), HER2+/ER- with anti-HER2+ ACT treatment (n = 110), HER2+/ER+ with anti-HER2 + ACT + endocrine treatment (n = 239), ER+/HER2-/LN- with endocrine treatment (n = 1113), ER+/HER2-/LN- with endocrine + ACT treatment (n = 243), ER+/HER2-/LN+ with endocrine treatment (n = 423), ER+/HER2-/LN+ with endocrine + ACT treatment (n = 433), and ER+/HER2-/LN- untreated (n = 200). Gene signature classification (e.g., proportion low-, high-risk) was generally well aligned with stratification based on current immunohistochemistry-based clinical practice. Most signatures did not provide any further risk stratification in TNBC and HER2+/ER- disease. Risk classifier agreement (low-, medium/intermediate-, high-risk groups) in ER+ assessment groups was on average 50-60% with occasional pair-wise comparisons having <30% agreement. Disregarding the intermediate-risk groups, the exact agreement between low- and high-risk groups was on average ~80-95%, for risk prediction signatures across all assessment groups. Outcome analyses were restricted to assessment groups of TNBC-ACT and endocrine treated ER+/HER2-/LN- and ER+/HER2-/LN+ cases. For ER+/HER2- disease, gene signatures appear to contribute additional prognostic value even at a relatively short follow-up time. Less apparent prognostic value was observed in the other groups for the tested signatures. The current study supports the usage of gene expression signatures in specific clinical treatment groups within population-based breast cancer. It also stresses the need of further development to reach higher consensus in individual patient classifications, especially for intermediate-risk patients, and the targeting of patients where current gene signatures and prognostic variables provide little support in clinical decision-making.

Ämnesord

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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