Dataset Information

Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer.

ABSTRACT:

Background

Breast cancer (BC) is the most common cancer in women, and despite the introduction of new screening programmes, therapies and monitoring technologies, there is still a need to develop more useful tests for monitoring treatment response and to inform clinical decision making. The purpose of this study was to compare circulating cell-free DNA (cfDNA) and circulating tumour cells (CTCs) with conventional breast cancer blood biomarkers (CA15-3 and alkaline phosphatase (AP)) as predictors of response to treatment and prognosis in patients with metastatic breast cancer (MBC).

Methods

One hundred ninety-four female patients with radiologically confirmed MBC were recruited to the study. Total cfDNA levels were determined by qPCR and compared with CELLSEARCH® CTC counts and CA15-3 and alkaline phosphatase (AP) values. Blood biomarker data were compared with conventional tumour markers, treatment(s) and response as assessed by RECIST and survival. Non-parametric statistical hypothesis tests were used to examine differences, correlation analysis and linear regression to determine correlation and to describe its effects, logistic regression and receiver operating characteristic curve (ROC curve) to estimate the strength of the relationship between biomarkers and clinical outcomes and value normalization against standard deviation to make biomarker values comparable. Kaplan-Meier estimator and Cox regression models were used to assess survival. Univariate and multivariate models were performed where appropriate.

Results

Multivariate analysis showed that both the amount of total cfDNA (p value?=?0.024, HR?=?1.199, CI?=?1.024-1.405) and the number of CTCs (p value?=?0.001, HR?=?1.243, CI?=?1.088-1.421) are predictors of overall survival (OS), whereas total cfDNA levels is the sole predictor for progression-free survival (PFS) (p value?=?0.042, HR?=?1.193, CI?=?1.007-1.415) and disease response when comparing response to non-response to treatment (HR?=?15.917, HR?=?12.481 for univariate and multivariate analysis, respectively). Lastly, combined analysis of CTCs and cfDNA is more informative than the combination of two conventional biomarkers (CA15-3 and AP) for prediction of OS.

Conclusion

Measurement of total cfDNA levels, which is a simpler and less expensive biomarker than CTC counts, is associated with PFS, OS and response in MBC, suggesting potential clinical application of a cheap and simple blood-based test.

SUBMITTER: Fernandez-Garcia D

PROVIDER: S-EPMC6924016 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer.

Fernandez-Garcia Daniel D Hills Allison A Page Karen K Hastings Robert K RK Toghill Bradley B Goddard Kate S KS Ion Charlotte C Ogle Olivia O Boydell Anna Rita AR Gleason Kelly K Rutherford Mark M Lim Adrian A Guttery David S DS Coombes R Charles RC Shaw Jacqueline A JA

Breast cancer research : BCR 20191219 1

<h4>Background</h4>Breast cancer (BC) is the most common cancer in women, and despite the introduction of new screening programmes, therapies and monitoring technologies, there is still a need to develop more useful tests for monitoring treatment response and to inform clinical decision making. The purpose of this study was to compare circulating cell-free DNA (cfDNA) and circulating tumour cells (CTCs) with conventional breast cancer blood biomarkers (CA15-3 and alkaline phosphatase (AP)) as pr ...[more]

PMID: 31856868

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Project description:BACKGROUND:The prognostic significance of plasma cell-free DNA (cfDNA) androgen receptor amplification (ARamp) in metastatic castration-resistant prostate cancer (mCRPC) compared with circulating tumor cell (CTC) counts is not known. METHODS:As part of correlative aims of a prospective study in mCRPC, concurrent and serial collections of plasma and CTCs were performed. Specimen collections were performed at baseline after progression on androgen deprivation therapy and then 12 weeks later. QuantStudio3D digital PCR system was used to determine plasma cfDNA AR copy number variations and Cell search assay for enumerating CTC counts. Association of baseline cfDNA ARamp status/CTC counts with overall survival (OS) (primary goal) was evaluated using Kaplan-Meier method and log-rank test (p???0.05 for significance) and receiver operator curves (ROCs) for ARamp status and CTC counts ?5. A multivariate analysis was performed using Cox regression models that included ARamp, CTC counts, and other clinical factors. RESULTS:ARamp was detected in 19/70 patients at baseline. At the time of analysis, 28/70 patients had died (median follow-up 806 days; interquartile range: 535-966). ARamp was associated with poor OS (2-year OS of 35% in ARamp vs. 71% in non-ARamp; log-rank p value ?0.0001). Baseline CTC counts ?5 (vs. <5) was also associated with poor survival (2-year OS of 44 vs. 74%; log-rank p?=?0.001). ROC analysis demonstrated area under the curve of 0.66 for ARamp-based prognosis and 0.68 for CTC count-based prognosis (p?=?0.84 for difference). The best two variables included for multivariable analysis were ARamp and CTC counts ?5; however, the two-factor model was not significantly better than using ARamp alone for predicting survival (hazard ratio?=?5.25; p?=?0.0002). CONCLUSIONS:CTCs and plasma cfDNA ARamp were observed to have equal prognostic value in mCRPC. Larger cohorts that incorporate molecular and clinical factors are needed to further refine prognosis in CRPC.

Dataset Information

Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer.

Background

Methods

Results

Conclusion

Publications

Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer.

Similar Datasets

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