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Sökning: L773:1661 3791 OR L773:1661 3805 > PITX2 DNA-Methylati...

PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients

Napieralski, R (författare)
Schricker, G (författare)
Auer, G (författare)
Karolinska Institutet
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Aubele, M (författare)
Perkins, J (författare)
Magdolen, V (författare)
Ulm, K (författare)
Hamann, M (författare)
Walch, A (författare)
Weichert, W (författare)
Kiechle, M (författare)
Wilhelm, OG (författare)
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 (creator_code:org_t)
2020-12-17
2021
Engelska.
Ingår i: Breast care (Basel, Switzerland). - : S. Karger AG. - 1661-3791 .- 1661-3805. ; 16:5, s. 523-531
Relaterad länk:
https://www.karger.c...
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http://kipublication...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • <b><i>Background:</i></b> 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. <b><i>Material and Methods:</i></b> 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. <b><i>Results:</i></b> 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; <i>p</i> = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR &#x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; <i>p</i> = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; <i>p</i> = 0.014). <b><i>Conclusion:</i></b> 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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