Zusammenfassung
GRUNDLAGEN: Die Überexpression von HER2 ist ein gut bekannter Risikofaktor einer schlechten Prognose beim metastasierten und frühen Brustkrebs. Um eine HER2-Positivität nachzuweisen, kann Tumorgewebe immunohistochemisch gefärbt werden oder durch Fluoreszenz-in-situ-Hybridisierung nachgewiesen werden. Es ist auch möglich, die extrazelluläre Domäne des HER2 (HER2/ECD)-Rezeptors durch eine Serumuntersuchung zu bestätigen. HER2/ECD korreliert gut mit einer schlechteren Prognose beim metastasierten und lokal fortgeschrittenen (Stadium III) Krebs, wenn die Serumkonzentration höher als 15 ng/ml ist, allerdings gibt es keine übereinstimmenden Daten für Patientinnen mit Brustkrebs in frühen Stadien. METHODIK UND ERGEBNISSE: 41 Personen mit Brustkrebs Stadium I und II und 52 gesunde Personen als Kontrollgruppe haben an der Studie teilgenommen. Vor der Operation wurde HER2/ECD ermittelt und mit HER2/neu-Überexpression, Ki67, Hormonrezeptorstatus und mit dem Stadium der Krankheit verglichen. Die durchschnittliche Serumkonzentration des HER2/ECD war bei den Patienten 8,62 ng/ml und 5,78 ng/ml bei der Kontrollgruppe, die Differenz war von statistischer Bedeutung (p = 0,000061). Der beste diagnostische Grenzwert war 7,7 ng/ml mit einer Sensitivität von 76,92 % und einer Spezifität von 72,92 %. Der positive Vorhersagewert des Tests war 69,77 %, der negative Vorhersagewert war 79,55 %. 74,71 % der Patienten waren richtig eingestuft. Serum HER2/ECD korrelierte gut mit dem Hormonrezeptorstatus, hatte aber eine negative Korrelation mit der histologischen Überexpression. SCHLUSSFOLGERUNG: Eine höhere Serumkonzentration als 7,7 ng/ml von HER2/ECD hat einen möglichen diagnostischen Wert im Stadium I und II bei Brustkrebs. Bei der Ermittlung von HER2-Positivität kann es nicht als ausschlaggebender Faktor verwendet werden. Die prognostische Bedeutung von HER2/ECD beim frühen Brustkrebs, die Korrelation mit dem Hormonrezeptorstatus und der Zusammenhang zwischen dem Hormonrezeptor und der HER2-Rezeptorsignalgebung müssen weiter analysiert werden, da diese therapeutische Implikationen haben könnte.
Summary
BACKGROUND: HER2 overexpression is well-established risk factor of worse prognosis in metastatic and early breast cancer. HER2 positivity can be determined from tumor tissue by immunohistochemical staining or by fluorescent in situ hybridization, or from serum by measuring concentration of HER2 receptor extracellular domain (HER2/ECD). HER2/ECD correlates well with worse prognosis in metastatic and locally advanced (stage III) disease if serum concentration is >15 ng/ml, but there are no consistent data for patients with early breast cancer. METHODS AND RESULTS: 41 patients with stage I and II breast cancer and 52 healthy controls were included into the study. HER2/ECD was determined before surgery and correlated with HER2/neu overexpression, Ki67, hormone receptor status and disease stage, and compared with value in healthy controls. Mean serum HER2/ECD concentration in patients was 8.62 ng/ml and 5.78 ng/ml in controls, and the difference was statistically significant (p = 0.000061). The best diagnostic cut-off value was 7.7 ng/ml, with 76.92% sensitivity and 72.92% specificity. Positive predictive value of the test was 69.77% and negative predictive value was 79.55%, with 74.71% of patients correctly classified. Serum HER2/ECD correlated with hormone receptors status, and no correlation with histological overexpression has been observed. CONCLUSION. Serum HER2/ECD concentration of ≥7.7 ng/ml has possible diagnostic value in stage I and II breast cancer. It should not be used as a determinant of HER2 positivity. Prognostic significance of HER2/ECD in early breast cancer, its correlation with hormone receptor status, and interconnection between hormone receptors and HER2 receptor signaling should be further analyzed, since it may have therapeutic implications.
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Badzek, S., Kelovic, V., Plestina, S. et al. Serum HER2/ECD value in stage I and II early breast cancer – need of a lower cut-off?. Wien Klin Wochenschr 123, 726–731 (2011). https://doi.org/10.1007/s00508-011-0099-4
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DOI: https://doi.org/10.1007/s00508-011-0099-4