Clinical Validation of PITX2 DNA Methylation to Predict Outcome in High-Risk Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy.

Schmitt, Manfred; Wilhelm, Olaf G; Noske, Aurelia; Schricker, Gabriele; Napieralski, Rudolph; Vetter, Martina; Aubele, Michaela; Perkins, Jonathan; Lauber, Jürgen; Ulm, Kurt; Thomssen, Christoph; Martens, John W M; Weichert, Wilko; Kiechle, Marion

doi:10.1159/000493016

2018

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Dokumenttyp:: Journal Article
Autor(en):: Schmitt, Manfred; Wilhelm, Olaf G; Noske, Aurelia; Schricker, Gabriele; Napieralski, Rudolph; Vetter, Martina; Aubele, Michaela; Perkins, Jonathan; Lauber, Jürgen; Ulm, Kurt; Thomssen, Christoph; Martens, John W M; Weichert, Wilko; Kiechle, Marion
Titel:: Clinical Validation of PITX2 DNA Methylation to Predict Outcome in High-Risk Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy.
Abstract:: Background: Breast cancer patients at high risk for recurrence are treated with anthracycline-based chemotherapy, but not all patients do equally benefit from such a regimen. To further improve therapy decision-making, biomarkers predicting outcome are of high unmet medical need. Methods: The percent DNA methylation ratio (PMR) of the promoter gene coding for the Paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time polymerase chain reaction (PCR) test. The multicenter study was conducted in routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue from 205 lymph node-positive breast cancer patients treated with adjuvant anthracycline-based chemotherapy. Results: The cut-off for the PITX2 methylation status (PMR = 12) was confirmed in a randomly selected cohort (n = 60) and validated (n = 145) prospectively with disease-free survival (DFS) at the 10-year follow-up. DFS was significantly different between the PMR ≤ 12 versus the PMR > 12 group with a hazard ratio (HR) of 2.74 (p < 0.001) in the validation cohort and also for the patient subgroup treated additionally with endocrine therapy (HR 2.47; p = 0.001). Conclusions: Early-stage lymph node-positive breast cancer patients with low PITX2 methylation do benefit from adjuvant anthracycline-based chemotherapy. Patients with a high PITX2 DNA methylation ratio, approximately 30%, show poor outcome and should thus be considered for alternative chemotherapy regimens.
Zeitschriftentitel:: Breast Care (Basel)
Jahr:: 2018
Band / Volume:: 13
Heft / Issue:: 6
Seitenangaben Beitrag:: 425-433
Volltext / DOI:: doi:10.1159/000493016
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/30800037
Print-ISSN:: 1661-3791
TUM Einrichtung:: Frauenklinik und Poliklinik; Institut für Medizinische Statistik und Epidemiologie
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