170P - Modification of methylation level DNA promoter in serum of a panel of gene before and after treatment and impact in prognostic factor in patients w...

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Breast Cancer
Translational Research
Presenter Joaquina Martinez-Galan
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors J. Martinez-Galan, C. Gonzalez-Rivas, J. Ruiz Vozmediano, L. Castillo, L. Ochoa, J.R. Delgado
  • Medical Oncology, Hospital Universitario Virgen de las Nieves, 18011 - Granada/ES



Alterations of genetic and epigenetic feature can provide important insghts into the natural history of breast cancer. Although DNA methylation analysis is a rapidly developing field, a reproducible epigenetic blood-based assay for diagnosis and follow up of breast cancer has yet to be successfully developed into a routine clinical test. The aim of ths study was to review DNA methylation of promoter methylation of 14.3.3 sigma and ESR1 in circulating DNA of breast cancer patients and to highlight the value of those novel biomarkers in prediction of therapeutic outcom


Plasma was sampled prospectively from 110 patients diagnosed of breast cancer. A PCR quantitative technique was used to analyzed the utility of circulating DNA with CpG island hypermethylation of ESR1, 14.3.3 sigma, APC and Rar Beta genes promoter regions as breast cancer biomarkers


The cutt-off points for the genes methylated promoters were established from the ROC curves, selecting values that gave the maximal likelihood ratio. Mean serum values of methylated genes before treatment was for ESR1:0.009 microg/ml, 14.3.3 sigma: 0.047 microg/ml, RarBeta: 0.0001 microg/ml and APC: 0.012 microg/ml. Mean values of methylated genes after treatment was for ESR: 0.003 microg/ml, 14.3.3 sigma: 0.038 microg/ml, RarBeta: 0 microg/ml and APC:0.001microg/ml. In the light of the discriminatory power of the ESR1 and 14.3.3 sigma and the finding that serum levels of methylated gene promoter changed after breast cancer treatment, post treatment modifications in these two promoters were analyzed. We observed lower methylated ESR1, 14.3.3 sigma and APC values after surgery respect pretreatment levels, but without an overall statistically significant difference. With a median follow up of 8 years we found that patients with a significant decrease of sera methylated levels of these genes after surgery had better interval free progression and overall survival respect patients without this observation.


These findings cast some doubts on the utility for early cancer diagnosis of highly sensitive techniques to identify hypermethylation os specific gene promoters in DNA extracted from serum. Althought numerous issues remain to be resolved the quantitative measurement of circulating methylated DNA is a promising tool for cancer prognostic assessment.


All authors have declared no conflicts of interest.