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• W2894301969 abstract "<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> The cut-off for the <i>PITX2</i> 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). <b>Conclusions:</b> Early-stage lymph node-positive breast cancer patients with low <i>PITX2</i> methylation do benefit from adjuvant anthracycline-based chemotherapy. Patients with a high <i>PITX2</i> DNA methylation ratio, approximately 30%, show poor outcome and should thus be considered for alternative chemotherapy regimens." @default.
• W2894301969 created "2018-10-05" @default.
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• W2894301969 date "2018-01-01" @default.
• W2894301969 modified "2023-09-23" @default.
• W2894301969 title "Clinical Validation of PITX2 DNA Methylation to Predict Outcome in High-Risk Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy" @default.
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• W2894301969 doi "https://doi.org/10.1159/000493016" @default.
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