%0 Journal Article
%@ 1465-542X
%A Varga, Zsuzsanna
%A Lebeau, Annette
%A Bu, Hong
%A Hartmann, Arndt
%A Penault-Llorca, Frederique
%A Guerini-Rocco, Elena
%A Schraml, Peter
%A Symmans, Fraser
%A Stoehr, Robert
%A Teng, Xiaodong
%A Turzynski, Andreas
%A von Wasielewski, Reinhard
%A Gürtler, Claudia
%A Laible, Mark
%A Schlombs, Kornelia
%A Joensuu, Heikki
%A Keller, Thomas
%A Sinn, Hans-Peter
%A Sahin, Ugur
%A Bartlett, John
%A Viale, Giuseppe
%C London
%D 2017
%F heidok:22945
%I BioMed Central
%J Breast Cancer Research
%N 55
%P 1-13
%T An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®
%U https://archiv.ub.uni-heidelberg.de/volltextserver/22945/
%V 19
%X Background: Accurate determination of the predictive markers human epidermal growth factor receptor 2 (HER2/ERBB2), estrogen receptor (ER/ESR1), progesterone receptor (PgR/PGR), and marker of proliferation Ki67 (MKI67) is indispensable for therapeutic decision making in early breast cancer. In this multicenter prospective study, we addressed the issue of inter- and intrasite reproducibility using the recently developed reverse transcription-quantitative real-time polymerase chain reaction-based MammaTyper® test.   Methods: Ten international pathology institutions participated in this study and determined messenger RNA expression levels of ERBB2, ESR1, PGR, and MKI67 in both centrally and locally extracted RNA from formalin-fixed, paraffin-embedded breast cancer specimens with the MammaTyper® test. Samples were measured repeatedly on different days within the local laboratories, and reproducibility was assessed by means of variance component analysis, Fleiss’ kappa statistics, and interclass correlation coefficients (ICCs).   Results: Total variations in measurements of centrally and locally prepared RNA extracts were comparable; therefore, statistical analyses were performed on the complete dataset. Intersite reproducibility showed total SDs between 0.21 and 0.44 for the quantitative single-marker assessments, resulting in ICC values of 0.980–0.998, demonstrating excellent agreement of quantitative measurements. Also, the reproducibility of binary single-marker results (positive/negative), as well as the molecular subtype agreement, was almost perfect with kappa values ranging from 0.90 to 1.00.   Conclusions: On the basis of these data, the MammaTyper® has the potential to substantially improve the current standards of breast cancer diagnostics by providing a highly precise and reproducible quantitative assessment of the established breast cancer biomarkers and molecular subtypes in a decentralized workup.