Dataset Information

CDO1 promoter methylation is a biomarker for outcome prediction of anthracycline treated, estrogen receptor-positive, lymph node-positive breast cancer patients.

ABSTRACT: BACKGROUND: Various biomarkers for prediction of distant metastasis in lymph-node negative breast cancer have been described; however, predictive biomarkers for patients with lymph-node positive (LNP) disease in the context of distinct systemic therapies are still very much needed. DNA methylation is aberrant in breast cancer and is likely to play a major role in disease progression. In this study, the DNA methylation status of 202 candidate loci was screened to identify those loci that may predict outcome in LNP/estrogen receptor-positive (ER+) breast cancer patients with adjuvant anthracycline-based chemotherapy. METHODS: Quantitative bisulfite sequencing was used to analyze DNA methylation biomarker candidates in a retrospective cohort of 162 LNP/ER+ breast cancer patients, who received adjuvant anthracycline-based chemotherapy. First, twelve breast cancer specimens were analyzed for all 202 candidate loci to exclude genes that showed no differential methylation. To identify genes that predict distant metastasis, the remaining loci were analyzed in 84 selected cases, including the 12 initial ones. Significant loci were analyzed in the remaining 78 independent cases. Metastasis-free survival analysis was conducted by using Cox regression, time-dependent ROC analysis, and the Kaplan-Meier method. Pairwise multivariate regression analysis was performed by linear Cox Proportional Hazard models, testing the association between methylation scores and clinical parameters with respect to metastasis-free survival. RESULTS: Of the 202 loci analysed, 37 showed some indication of differential DNA methylation among the initial 12 patient samples tested. Of those, 6 loci were associated with outcome in the initial cohort (n = 84, log rank test, p < 0.05).Promoter DNA methylation of cysteine dioxygenase 1 (CDO1) was confirmed in univariate and in pairwise multivariate analysis adjusting for age at surgery, pathological T stage, progesterone receptor status, grade, and endocrine therapy as a strong and independent biomarker for outcome prediction in the independent validation set (log rank test p-value = 0.0010). CONCLUSIONS: CDO1 methylation was shown to be a strong predictor for distant metastasis in retrospective cohorts of LNP/ER+ breast cancer patients, who had received adjuvant anthracycline-based chemotherapy.

SUBMITTER: Dietrich D

PROVIDER: S-EPMC2893112 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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CDO1 promoter methylation is a biomarker for outcome prediction of anthracycline treated, estrogen receptor-positive, lymph node-positive breast cancer patients.

Dietrich Dimo D Krispin Manuel M Dietrich Jörn J Fassbender Anne A Lewin Jörn J Harbeck Nadia N Schmitt Manfred M Eppenberger-Castori Serenella S Vuaroqueaux Vincent V Spyratos Frédérique F Foekens John A JA Lesche Ralf R Martens John W M JW

BMC cancer 20100601

<h4>Background</h4>Various biomarkers for prediction of distant metastasis in lymph-node negative breast cancer have been described; however, predictive biomarkers for patients with lymph-node positive (LNP) disease in the context of distinct systemic therapies are still very much needed. DNA methylation is aberrant in breast cancer and is likely to play a major role in disease progression. In this study, the DNA methylation status of 202 candidate loci was screened to identify those loci that m ...[more]

PMID: 20515469

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Project description:BackgroundCurrent chemoradiation regimens for locally advanced cervical cancer are fairly uniform despite a profound diversity of treatment response and recurrence patterns. The wide range of treatment responses and prognoses to standardized concurrent chemoradiation highlights the need for a reliable tool to predict treatment outcomes. We investigated pretreatment magnetic resonance (MR) imaging features of primary tumor and involved lymph node for predicting clinical outcome in cervical cancer patients.MethodsWe included 93 node-positive cervical cancer patients treated with definitive chemoradiotherapy at our institution between 2006 and 2017. The median follow-up period was 38?months (range, 5-128). Primary tumor and involved lymph node were manually segmented on axial gadolinium-enhanced T1-weighted images as well as T2-weighted images and saved as 3-dimensional regions of interest (ROI). After the segmentation, imaging features related to histogram, shape, and texture were extracted from each ROI. Using these features, random survival forest (RSF) models were built to predict local control (LC), regional control (RC), distant metastasis-free survival (DMFS), and overall survival (OS) in the training dataset (n?=?62). The generated models were then tested in the validation dataset (n?=?31).ResultsFor predicting LC, models generated from primary tumor imaging features showed better predictive performance (C-index, 0.72) than those from lymph node features (C-index, 0.62). In contrast, models from lymph nodes showed superior performance for predicting RC, DMFS, and OS compared to models of the primary tumor. According to the 3-year time-dependent receiver operating characteristic analysis of LC, RC, DMFS, and OS prediction, the respective area under the curve values for the predicted risk of the models generated from the training dataset were 0.634, 0.796, 0.733, and 0.749 in the validation dataset.ConclusionsOur results suggest that tumor and lymph node imaging features may play complementary roles for predicting clinical outcomes in node-positive cervical cancer.

Project description:ImportanceOvertreatment of early-stage breast cancer with favorable tumor biology in older patients may be harmful without affecting recurrence and survival. Guidelines that recommend deimplementation of sentinel lymph node biopsy (SLNB) (Choosing Wisely) and radiotherapy (RT) (National Comprehensive Cancer Network) have been published.ObjectiveTo describe the use rates and association with disease recurrence of SLNB and RT in older women with breast cancer.Design, setting, and participantsThis cohort study obtained patient and clinical data from an integrated cancer registry and electronic health record of a single health care system in Pennsylvania. The cohort was composed of consecutive female patients 70 years or older who were diagnosed with early-stage, estrogen receptor-positive, ERBB2 (formerly HER2)-negative, clinically node-negative breast cancer from January 1, 2010, to December 31, 2018, who were treated at 15 community and academic hospitals within the health system.ExposuresSentinel lymph node biopsy and adjuvant RT.Main outcomes and measuresPrimary outcomes were 5-year locoregional recurrence-free survival (LRFS) rate and disease-free survival (DFS) rate after SLNB and after RT. Secondary outcomes included recurrence rate, subgroups that may benefit from SLNB or RT, and use rate of SLNB and RT over time. Propensity scores were used to create 2 cohorts to separately evaluate the association of SLNB and RT with recurrence outcomes. Cox proportional hazards regression model was used to estimate hazard ratios (HRs).ResultsFrom 2010 to 2018, a total of 3361 women 70 years or older (median [interquartile range {IQR}] age, 77.0 [73.0-82.0] years) with estrogen receptor-positive, ERBB2-negative, clinically node-negative breast cancer were included in the study. Of these women, 2195 (65.3%) received SLNB and 1828 (54.4%) received adjuvant RT. Rates of SLNB steadily increased (1.0% per year), a trend that persisted after the 2016 adoption of the Choosing Wisely guideline. Rates of RT decreased slightly (3.4% per year). To examine patient outcomes and maximize follow-up time, the analysis was limited to cases from 2010 to 2014, identifying 2109 patients with a median (IQR) follow-up time of 4.1 (2.5-5.7) years. In the propensity score-matched cohorts, no association was found between SLNB and either LRFS (HR, 1.26; 95% CI, 0.37-4.30; P = .71) or DFS (HR, 1.92; 95% CI, 0.86-4.32; P = .11). In addition, RT was not associated with LRFS (HR, 0.33; 95% CI, 0.09-1.24; P = .10) or DFS (HR, 0.99; 95% CI, 0.46-2.10; P = .97). Subgroup analysis showed that stratification by tumor grade or comorbidity was not associated with LRFS or DFS. Low absolute rates of recurrence were observed when comparing the groups that received SLNB (3.5%) and those that did not (4.5%) as well as the groups that received RT (2.7%) and those that did not (5.5%).Conclusions and relevanceThis study found that receipt of SLNB or RT was not associated with improved LRFS or DFS in older patients with ER-positive, clinically node-negative breast cancer. Despite limited follow-up time and wide 95% CIs, this study supports the continued deimplementation of both SLNB and RT in accordance with the Choosing Wisely and National Comprehensive Cancer Network guidelines.

Dataset Information

CDO1 promoter methylation is a biomarker for outcome prediction of anthracycline treated, estrogen receptor-positive, lymph node-positive breast cancer patients.

Publications

CDO1 promoter methylation is a biomarker for outcome prediction of anthracycline treated, estrogen receptor-positive, lymph node-positive breast cancer patients.

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