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PITX2 DNA-methylation predicts response to anthracycline-based adjuvant chemotherapy in triple-negative breast cancer patients.
Int. J. Oncol. 52, 755-767 (2018)
Triple-negative breast cancer (TNBC) constitutes a heterogeneous breast cancer subgroup with poor prognosis; survival rates are likely to be lower with TNBC compared to other breast cancer subgroups. For this disease, systemic adjuvant chemotherapy regimens often yield suboptimal clinical results. To improve treatment regimens in TNBC, identification of molecular biomarkers may help to select patients for individualized adjuvant therapy. Evidence has accumulated that determination of the methylation status of the PITX2 gene provides a predictive value in various breast cancer subgroups, either treated with endocrine-based therapy or anthracycline-containing chemotherapy. To further explore the validity of this novel predictive candidate biomarker, in the present exploratory retrospective study, determination of the PITX2 DNA-methylation status was assessed for non-metastatic TNBC patients treated with adjuvant anthracycline-based chemotherapy by molecular analysis of breast cancer tissues. The PITX2 DNA-methylation status was determined in fresh-frozen tumor tissue specimens (n=56) by methylation-specific qRT-PCR (qMSP) and the data related to disease-free and overall survival, applying an optimized DNA-methylation score of 6.35%. For non-metastatic TNBC patients treated with adjuvant systemic anthracycline-based chemotherapy, a low PITX2 DNA-methylation status (<6.35) defines TNBC patients with poor disease-free and overall survival. Univariate and multivariate analyses demonstrate the statistically independent predictive value of PITX2 DNA-methylation. For non-metastatic TNBC patients, selective determination of the PITX2 DNA-methylation status may serve as a cancer biomarker for predicting response to anthracycline-based adjuvant chemotherapy. The assay based on methylation of the PIXT2 gene can be applied to frozen and routinely available formalin-fixed, paraffin-embedded (FFPE) breast cancer tumor tissues that will not only define those TNBC patients who may benefit from anthracycline-based chemotherapy but also those who should be spared the necessity of such potentially toxic treatment. Such patients should be allocated to alternative treatment options.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Pitx2 ; Triple-negative Breast Cancer ; Anthracycline ; Dna-methylation ; Therapy Response Prediction ; Biomarker; Left-right Asymmetry; Clinical-practice Guideline; Eortc Pathobiology-group; Squamous-cell Carcinoma; Embryonic-development; Shox2 Methylation; American Society; Targeted Therapy; Prostate-cancer; Neoadjuvant
ISSN (print) / ISBN
1019-6439
e-ISSN
1791-2423
Quellenangaben
Volume: 52,
Issue: 3,
Pages: 755-767
Publisher
Spandidos Publ.
Publishing Place
Athens
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Analytical Pathology (AAP)