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

Clin Breast Cancer. 2020 Apr;20(2):108-116. doi: 10.1016/j.clbc.2019.07.003. Epub 2019 Aug 22.

Abstract

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 × 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).

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.

Keywords: Breast Cancer; CA 15-3; Plasma Biomarkers; Prognosis; miR-923.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / blood
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery*
  • 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
  • Mucin-1 / blood
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / prevention & control
  • Oligonucleotide Array Sequence Analysis
  • Predictive Value of Tests
  • Prognosis
  • ROC Curve
  • Risk Assessment / methods

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • MUC1 protein, human
  • MicroRNAs
  • Mucin-1