title: Assessing HER2 testing quality in breast cancer: variables that influence HER2 positivity rate from a large, multicenter, observational study in Germany.
abstract: Despite >10 years of routine human epidermal growth factor receptor 2 (HER2) testing in breast cancer, testing quality is still an issue. Guidelines recommend assessing HER2 positivity rates as a quality indicator; however, the extent to which patient- or tumor-related factors influence HER2 positivity is still unknown. The present study analyzed these influences to identify pathology centers with HER2 positivity rates unexplained by patient- or tumor-related factors. This observational, prospective study monitored routine HER2 testing at 57 institutes of pathology in Germany (January 2013-August 2014). Data collected included HER2 test result, patient- and tumor-related factors, sample source, and method of sample retrieval. Factors influencing HER2 positivity rates were identified by multiple logistic regression. Individual center effects were assessed in an extended multiple logistic regression model by their statistical significance after adjusting for the combined effect of patient- or tumor-related covariates and multiple testing. Analyses included 15 332 invasive breast cancer samples. Histologic grade showed the strongest influence on HER2 positivity, followed by hormone receptor status, histologic subtype, age, and nodal status (all P<0.0001). The overall HER2 positivity rate across centers was 14.4% (range 7.1-27.3%). A statistically significant center effect on the HER2 positivity rate was identified for three centers (P<0.05), with a trend toward a center effect for a further three (P<0.2). This study, the first of its kind, highlights that assessing HER2 testing quality with HER2 positivity rates should include standardized assessment of patient- or tumor-related characteristics to identify centers with HER2 testing quality issues more effectively. As treatment options for HER2-positive breast cancer continue to evolve, identifying the right patients is key.
authors: Institut für Pathologie Nordhessen and Targos Molecular Pathology GmbH, Kassel, Germany.
authors: Josef
authors: J
authors: Rüschoff
authors: Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; Gemeinschaftspraxis für Pathologie, Lübeck, Germany.
authors: Annette
authors: A
authors: Lebeau
authors: Institut für Pathologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors: Hans
authors: H
authors: Kreipe
authors: Sektion Gynäkopathologie, Pathologische Institut, Heidelberg, Germany.
authors: Peter
authors: P
authors: Sinn
authors: Institute of Pathology, Evangelical Bethesda Clinical Center, Duisburg, Germany.
authors: Claus Dieter
authors: CD
authors: Gerharz
authors: Biostatistical Data Services Koch, Schwetzingen, Germany.
authors: Winfried
authors: W
authors: Koch
authors: Roche Pharma AG, Grenzach-Wyhlen, Germany.
authors: Stefanie
authors: S
authors: Morris
authors: Roche Pharma AG, Grenzach-Wyhlen, Germany.
authors: Johannes
authors: J
authors: Ammann
authors: Clinic for Gynecology, Gynecologic Oncology, and Obstetrics, Breast Cancer Center, Berlin, Germany.
authors: Michael
authors: M
authors: Untch
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005858:Germany; D006801:Humans; D060787:Neoplasm Grading; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human