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PITX2 DNA-methylation: Predictive versus prognostic value for anthracycline-based chemotherapy in triple-negative breast cancer patients.
Breast Care 16, 523-531 (2021)
Background: PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. Material and Methods: The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. Results: The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; p = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR >2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; p = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; p = 0.014). Conclusion: In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Anthracyclines ; Biomarker ; Chemotherapy ; Dna Methylation ; Homeodomain Proteins/genetics ; Pitx2 ; Therapy Prediction ; Treatment Outcome ; Triple-negative Breast Cancer/neoplasms ; Tumor/genetics; Adjuvant Chemotherapy; Clinical Validation; Cell; Multicenter; Activation; Biomarker; Pathway; Marker; Risk
ISSN (print) / ISBN
1661-3791
e-ISSN
1661-3805
Journal
Breast Care
Quellenangaben
Volume: 16,
Issue: 5,
Pages: 523-531
Publisher
Karger
Publishing Place
Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Analytical Pathology (AAP)
Grants
Therawis Diagnostics GmbH