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Clinical Value of R...
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Brueffer, ChristianLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Translational Oncogenomics,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
(author)
Clinical Value of RNA Sequencing–Based Classifiers for Prediction of the Five Conventional Breast Cancer Biomarkers: A Report From the Population-Based Multicenter Sweden Cancerome Analysis Network—Breast Initiative
- Article/chapterEnglish2018
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LIBRIS-ID:oai:lup.lub.lu.se:6ef6701b-efc7-492b-a141-ad068571e7b9
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https://lup.lub.lu.se/record/6ef6701b-efc7-492b-a141-ad068571e7b9URI
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https://doi.org/10.1200/PO.17.00135DOI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
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PurposeIn early breast cancer (BC), five conventional biomarkers—estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki67, and Nottingham histologic grade (NHG)—are used to determine prognosis and treatment. We aimed to develop classifiers for these biomarkers that were based on tumor mRNA sequencing (RNA-seq), compare classification performance, and test whether such predictors could add value for risk stratification.MethodsIn total, 3,678 patients with BC were studied. For 405 tumors, a comprehensive multi-rater histopathologic evaluation was performed. Using RNA-seq data, single-gene classifiers and multigene classifiers (MGCs) were trained on consensus histopathology labels. Trained classifiers were tested on a prospective population-based series of 3,273 BCs that included a median follow-up of 52 months (Sweden Cancerome Analysis Network—Breast [SCAN-B], ClinicalTrials.gov identifier: NCT02306096), and results were evaluated by agreement statistics and Kaplan-Meier and Cox survival analyses.ResultsPathologist concordance was high for ER, PgR, and HER2 (average κ, 0.920, 0.891, and 0.899, respectively) but moderate for Ki67 and NHG (average κ, 0.734 and 0.581). Concordance between RNA-seq classifiers and histopathology for the independent cohort of 3,273 was similar to interpathologist concordance. Patients with discordant classifications, predicted as hormone responsive by histopathology but non–hormone responsive by MGC, had significantly inferior overall survival compared with patients who had concordant results. This extended to patients who received no adjuvant therapy (hazard ratio [HR], 3.19; 95% CI, 1.19 to 8.57), or endocrine therapy alone (HR, 2.64; 95% CI, 1.55 to 4.51). For cases identified as hormone responsive by histopathology and who received endocrine therapy alone, the MGC hormone-responsive classifier remained significant after multivariable adjustment (HR, 2.45; 95% CI, 1.39 to 4.34).ConclusionClassification error rates for RNA-seq–based classifiers for the five key BC biomarkers generally were equivalent to conventional histopathology. However, RNA-seq classifiers provided added clinical value in particular for tumors determined by histopathology to be hormone responsive but by RNA-seq to be hormone insensitive.
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Vallon-Christersson, JohanLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-jvc
(author)
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Grabau, DortheSkåne University Hospital(Swepub:lu)med-dgu
(author)
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Ehinger, AnnaLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Individuell Bröstcancerbehandling,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Personalized Breast Cancer Treatment,Lund University Research Groups,Blekinge Hospital,Skåne University Hospital(Swepub:lu)pat-amm
(author)
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Häkkinen, JariLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)thep-jha
(author)
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Hegardt, CeciliaLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)zoof-che
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Malina, JanneSkåne University Hospital
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Chen, YilunLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Translational Oncogenomics,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups(Swepub:lu)med-yic
(author)
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Bendahl, Pär-OlaLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Individuell Bröstcancerbehandling,Forskargrupper vid Lunds universitet,The Liquid Biopsy och Tumörprogression i Bröstcancer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Personalized Breast Cancer Treatment,Lund University Research Groups,The Liquid Biopsy and Tumor Progression in Breast Cancer(Swepub:lu)onk-pbe
(author)
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Manjer, JonasLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital(Swepub:lu)smi-jma
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Malmberg, MartinSkåne University Hospital
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Larsson, ChristerLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Tumörcellsbiologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Tumor Cell Biology,Lund University Research Groups(Swepub:lu)molm-cla
(author)
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Loman, NiklasLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancer-genetik,Institutionen för kliniska vetenskaper, Lund,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Breastcancer-genetics,Department of Clinical Sciences, Lund,Skåne University Hospital(Swepub:lu)onk-nlo
(author)
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Rydén, LisaLund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Bröstcancerkirurgi,Forskargrupper vid Lunds universitet,The Liquid Biopsy och Tumörprogression i Bröstcancer,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Breast Cancer Surgery,Lund University Research Groups,The Liquid Biopsy and Tumor Progression in Breast Cancer,Skåne University Hospital(Swepub:lu)pat-lry
(author)
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Borg, ÅkeLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups(Swepub:lu)onk-abo
(author)
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Saal, Lao H.Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Translational Oncogenomics,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups(Swepub:lu)onk-ls0
(author)
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Bröstcancer-genetikSektion I
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In:JCO Precision Oncology2, s. 1-182473-4284
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