Statistical modelling of HER2-positivity in breast cancer: Final analyses from two large, multicentre, non-interventional studies in Germany
Background: The German NIU HER2 model was developed based on five variables found to have statistically significant influences on HER2-positivity, to allow exploration of deviations between model-predicted and actual HER2-positivity rates as a measure of testing quality. The prospective, non-interve...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-02-01
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| Series: | Breast |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0960977619311129 |
| _version_ | 1818188923323547648 |
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| author | Josef Rüschoff Annette Lebeau Peter Sinn Hans-Ulrich Schildhaus Thomas Decker Johannes Ammann Claudia Künzel Winfried Koch Michael Untch |
| author_facet | Josef Rüschoff Annette Lebeau Peter Sinn Hans-Ulrich Schildhaus Thomas Decker Johannes Ammann Claudia Künzel Winfried Koch Michael Untch |
| author_sort | Josef Rüschoff |
| collection | DOAJ |
| description | Background: The German NIU HER2 model was developed based on five variables found to have statistically significant influences on HER2-positivity, to allow exploration of deviations between model-predicted and actual HER2-positivity rates as a measure of testing quality. The prospective, non-interventional EPI HER2 BC study (NCT02666261) compared NIU and EPI data, aiming to validate the NIU model. Methods: HER2 status and patient-/tumour-related information were collected from eligible patients with invasive breast cancer. The influence of variables on HER2-positivity was compared between studies and the NIU model validated using EPI data with cut-off and variable coefficients from the NIU study. The influences of additional variables, centre effects and laboratory-specific parameters were also explored. Results: The study included 14,729 EPI and 15,281 NIU samples; HER2-positivity rates were comparable (13.5% versus 14.2%). The five covariates from NIU were shown to significantly affect HER2-positivity using EPI data. The Youden Index for the NIU model refitted to EPI data (0.3632) and the NIU model for prediction of HER2-positivity in EPI (0.3552) was close to that for the NIU model fitted to NIU data (0.3888), validating the NIU model. Replacing hormone receptor status with progesterone and oestrogen receptor expression, and adding method of sample extraction as a variable improved the model’s predictive strength (ROC AUC 0.7402; Youden Index 0.3935). Conclusions: Reliable, high-quality HER2-testing methods are essential for selection of patients with HER2-positive breast cancer for HER2-tageted treatment. Integration of our model into a locally used software or website may improve its viability for use in clinical practice. |
| first_indexed | 2024-12-11T23:34:38Z |
| format | Article |
| id | doaj.art-031761f292f54ba593fe8d88242c9b41 |
| institution | Directory Open Access Journal |
| issn | 1532-3080 |
| language | English |
| last_indexed | 2024-12-11T23:34:38Z |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Breast |
| spelling | doaj.art-031761f292f54ba593fe8d88242c9b412022-12-22T00:45:54ZengElsevierBreast1532-30802020-02-0149246253Statistical modelling of HER2-positivity in breast cancer: Final analyses from two large, multicentre, non-interventional studies in GermanyJosef Rüschoff0Annette Lebeau1Peter Sinn2Hans-Ulrich Schildhaus3Thomas Decker4Johannes Ammann5Claudia Künzel6Winfried Koch7Michael Untch8Institut für Pathologie Nordhessen and Targos Molecular Pathology GmbH, Germaniastr. 7, D-34119, Kassel, Germany; Corresponding author.Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany; Gemeinschaftspraxis für Pathologie, Pferdemarkt 12, 23552, Lübeck, GermanySektion Gynäkopathologie, Pathologisches Institut der Universität Heidelberg, Im Neuenheimer Feld 224, 69124, Heidelberg, GermanyInstitute of Pathology, University Medical Center Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, GermanyDepartment of Surgical Pathology, Dietrich Bonhoeffer Medical Center, Allendestrasse 30, 17036, Neubrandenburg, GermanyRoche Pharma AG, Emil-Barell-Str. 1, 79639, Grenzach-Wyhlen, GermanyRoche Pharma AG, Emil-Barell-Str. 1, 79639, Grenzach-Wyhlen, GermanyBDS Koch, Bibienastraße 5, 68723, Schwetzingen, GermanyHELIOS Klinikum Berlin-Buch, Schwanebecker Chaussee 50, D-13125, Berlin, GermanyBackground: The German NIU HER2 model was developed based on five variables found to have statistically significant influences on HER2-positivity, to allow exploration of deviations between model-predicted and actual HER2-positivity rates as a measure of testing quality. The prospective, non-interventional EPI HER2 BC study (NCT02666261) compared NIU and EPI data, aiming to validate the NIU model. Methods: HER2 status and patient-/tumour-related information were collected from eligible patients with invasive breast cancer. The influence of variables on HER2-positivity was compared between studies and the NIU model validated using EPI data with cut-off and variable coefficients from the NIU study. The influences of additional variables, centre effects and laboratory-specific parameters were also explored. Results: The study included 14,729 EPI and 15,281 NIU samples; HER2-positivity rates were comparable (13.5% versus 14.2%). The five covariates from NIU were shown to significantly affect HER2-positivity using EPI data. The Youden Index for the NIU model refitted to EPI data (0.3632) and the NIU model for prediction of HER2-positivity in EPI (0.3552) was close to that for the NIU model fitted to NIU data (0.3888), validating the NIU model. Replacing hormone receptor status with progesterone and oestrogen receptor expression, and adding method of sample extraction as a variable improved the model’s predictive strength (ROC AUC 0.7402; Youden Index 0.3935). Conclusions: Reliable, high-quality HER2-testing methods are essential for selection of patients with HER2-positive breast cancer for HER2-tageted treatment. Integration of our model into a locally used software or website may improve its viability for use in clinical practice.http://www.sciencedirect.com/science/article/pii/S0960977619311129Invasive breast cancerHER2ImmunohistochemistryIn situ hybridisationQuality controlStatistical modelling |
| spellingShingle | Josef Rüschoff Annette Lebeau Peter Sinn Hans-Ulrich Schildhaus Thomas Decker Johannes Ammann Claudia Künzel Winfried Koch Michael Untch Statistical modelling of HER2-positivity in breast cancer: Final analyses from two large, multicentre, non-interventional studies in Germany Breast Invasive breast cancer HER2 Immunohistochemistry In situ hybridisation Quality control Statistical modelling |
| title | Statistical modelling of HER2-positivity in breast cancer: Final analyses from two large, multicentre, non-interventional studies in Germany |
| title_full | Statistical modelling of HER2-positivity in breast cancer: Final analyses from two large, multicentre, non-interventional studies in Germany |
| title_fullStr | Statistical modelling of HER2-positivity in breast cancer: Final analyses from two large, multicentre, non-interventional studies in Germany |
| title_full_unstemmed | Statistical modelling of HER2-positivity in breast cancer: Final analyses from two large, multicentre, non-interventional studies in Germany |
| title_short | Statistical modelling of HER2-positivity in breast cancer: Final analyses from two large, multicentre, non-interventional studies in Germany |
| title_sort | statistical modelling of her2 positivity in breast cancer final analyses from two large multicentre non interventional studies in germany |
| topic | Invasive breast cancer HER2 Immunohistochemistry In situ hybridisation Quality control Statistical modelling |
| url | http://www.sciencedirect.com/science/article/pii/S0960977619311129 |
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