%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.