A Predictor of Early Disease Recurrence in Patients With Breast Cancer Using a Cell-free RNA and Protein Liquid Biopsy

Circulating biomarkers have been increasingly used in the clinical management of breast cancer. The present study evaluated whether RNAs and a protein present in the plasma of patients with breast cancer might have utility as prognostic biomarkers complementary to existing clinical tests. We perform...

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Bibliographic Details
Published in:Clinical breast cancer 2020-04, Vol.20 (2), p.108-116
Main Authors: Lasham, Annette, Fitzgerald, Sandra J., Knowlton, Nicholas, Robb, Tamsin, Tsai, Peter, Black, Michael A., Williams, Liam, Mehta, Sunali Y., Harris, Gavin, Shelling, Andrew N., Blenkiron, Cherie, Print, Cristin G.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor - blood
Biomarkers, Tumor - metabolism
Breast Cancer
Breast Neoplasms - blood
Breast Neoplasms - pathology
Breast Neoplasms - surgery
CA 15-3
Case-Control Studies
Cell-Free Nucleic Acids - blood
Cell-Free Nucleic Acids - metabolism
Disease-Free Survival
Female
Gene Expression Profiling
Healthy Volunteers
Humans
Kaplan-Meier Estimate
Liquid Biopsy - methods
Mastectomy
MicroRNAs - blood
Middle Aged
miR-923
Mucin-1 - blood
Neoplasm Recurrence, Local - epidemiology
Neoplasm Recurrence, Local - genetics
Neoplasm Recurrence, Local - prevention & control
Oligonucleotide Array Sequence Analysis
Plasma Biomarkers
Predictive Value of Tests
Prognosis
Risk Assessment - methods
ROC Curve
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Summary:Circulating biomarkers have been increasingly used in the clinical management of breast cancer. The present study evaluated whether RNAs and a protein present in the plasma of patients with breast cancer might have utility as prognostic biomarkers complementary to existing clinical tests. We performed microarray profiling of small noncoding RNAs in plasma samples from 30 patients with breast cancer and 10 control individuals. Two small noncoding RNAs, including microRNA (miR)-923, were selected and quantified in plasma samples from an evaluation cohort of 253 patients with breast cancer, using droplet digital polymerase chain reaction. We also measured cancer antigen (CA) 15-3 protein levels in these samples. Cox regression survival analysis was used to determine which markers were associated with patient prognosis. As independent markers of prognosis, the plasma levels of miR-923 and CA 15-3 at the time of surgery for breast cancer were significantly associated with prognosis, irrespective of treatment (Cox proportional hazards, P = 3.9 × 10−3 and 1.9 × 10−9, respectively). After building a multivariable model with standard clinical and pathological features, the addition of miR-923 and CA 15-3 information into the model resulted in a significantly better predictor of disease recurrence in patients, irrespective of treatment, compared with the use of clinicopathological data alone (area under the curve at 3 years, 0.858 vs. 0.770 with clinicopathological markers only; P = .017). We propose that the plasma levels of miR-923 and CA 15-3, combined with standard clinicopathological predictors, could be used as a preoperative, noninvasive estimate of patient prognosis to identify which women might need more aggressive treatment or closer surveillance after surgery for breast cancer. To assist clinicians with treatment decisions for patients with breast cancer, we investigated whether the preoperative plasma levels of RNAs and the protein cancer antigen 15-3 were associated with prognosis. We identified a novel biomarker, microRNA-923, and combined this with cancer antigen 15-3 and clinicopathological features to build a multivariable model predictive of prognosis, irrespective of treatment, in 253 patients with breast cancer.
ISSN:1526-8209
1938-0666
DOI:10.1016/j.clbc.2019.07.003