Abstract
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.
Introduction: 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. Patients and Methods: 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. Results: 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 x 10(-3) and 1.9 x 10(-9), respectively). After building a multivariable model with standard clinical and pathological features, the addition of miR923 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). Conclusion: 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. (C) 2019 Elsevier Inc. All rights reserved.