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DNA Methylation Prfle Predicts Recurrence Risk:Tam/BCa

DNA methylation profile predicts risk of recurrence in tamoxifen-treated, node-negative breast cancer patients.

S. Maier, I. Nimmrich, A. Marx, S. Eppenberger-Castori, F. Jaenicke, A. Paradiso, F. Spyratos, J. Foekens, M. Schmitt, N. Harbeck;

Epigenomics AG, Berlin, Germany; Stiftung Tumorbank, Basel, Switzerland; University Hospital Eppendorf, Hamburg, Germany; National Cancer Institute, Bari, Italy; Centre René Huguenin, St. Cloud, France; Erasmus Medical Center, Rotterdam, Netherlands; Technical University, Munich, Germany

Abstract: Background: Today, many women with node-negative, hormone receptor positive breast cancer receive adjuvant chemotherapy followed by endocrine therapy.

However, the majority of these patients would never have experienced a relapse and would have been sufficiently treated with endocrine therapy alone. Aim of our study was to identify DNA methylation markers associated with a low risk of recurrence after tamoxifen monotherapy.

Methods: As a first step, we performed a genome-wide screening for DNA methylation markers associated with the risk of recurrence after tamoxifen monotherapy. The best candidates were then validated in a population of 278 patients using a microarray approach.

Results: We identified several DNA methylation markers with a strong relation to clinical outcome (cox proportional hazard model, p<0.05). In a multivariate model, DNA methylation contributed significant information to conventional factors such as grade, tumor size, or estrogen receptor expression level.

Furthermore, by combining three markers into a methylation score and defining a cut-off, we identified a group with excellent outcome when treated with tamoxifen alone (disease-free survival 95 % at 10 years, versus 62 % in the poor prognosis group). Validation in an independent patient cohort is currently in progress. So far, the best marker has already been validated (p<0.05).

Conclusions: These results provide substantial evidence that DNA methylation could be used to predict outcome in node-negative patients with tamoxifen monotherapy, and to identify low risk groups which may not require additional cytotoxic treatment.

Abstract No: 525

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