Association of Serum Progranulin Levels With Disease Progression, Therapy Response and Survival in Patients With Metastatic Breast Cancer

Clin Breast Cancer. 2020 Jun;20(3):220-227. doi: 10.1016/j.clbc.2019.11.010. Epub 2019 Dec 5.

Abstract

Background: Progranulin (GP88) is a critical player in breast tumorigenesis. GP88 tumor expression is associated with increased recurrence and mortality, whereas GP88 circulating levels are elevated in patients with breast cancer compared with healthy individuals. We examined here the correlation between serum GP88 levels in patients with metastatic breast cancer (MBC) with overall survival and disease status determined as response to therapy or progression of disease.

Patients and methods: An institutional review board (IRB)-approved study prospectively enrolled 101 patients with MBC at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. GP88 serum levels were correlated with patients' disease status determined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and survival outcomes by Kaplan-Meier analysis and log rank statistics.

Results: Patients' survival was stratified by serum GP88 level. Patients with serum GP88 < 55 ng/mL had a 4-fold increased survival compared with patients with GP88 > 55 ng/mL. Examination of GP88 serum levels in association with disease status showed a statistically significant association between serum GP88 levels and disease progression or response to therapy while CA15-3 level was only associated to progression.

Conclusion: The association of serum GP88 level with survival and disease status suggests the potential of using the serum GP88 test for monitoring disease status in patients with MBC. Measurement of serum GP88 levels in patients with MBC may have clinical value as a cost-effective adjunct to the management of patients with MBC with imaging.

Keywords: CA15-3; Disease monitoring; GP88; Measurement of response to therapy; Serum GP88 enzyme immunoassay for disease monitoring.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Breast Neoplasms / blood*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / mortality
  • Breast Neoplasms / therapy
  • Disease Progression
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Mastectomy
  • Middle Aged
  • Mucin-1 / blood
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / prevention & control
  • Predictive Value of Tests
  • Progranulins / blood*
  • Prospective Studies
  • Radiotherapy, Adjuvant
  • Response Evaluation Criteria in Solid Tumors

Substances

  • Biomarkers, Tumor
  • GRN protein, human
  • MUC1 protein, human
  • Mucin-1
  • Progranulins