Abstract P2-02-10: Circulating level of GP88/Progranulin is associated with clinical outcome and overall survival in stage 4 breast cancer patients
Authors: Serrero G , Hawkins D , Hicks D , Rosenblatt P , Tait N , Yue B , Tkaczuk K 
Published: February 2018

Monitoring of disease status in metastatic breast cancer (MBC) patients is a necessary step for an optimal management of patients during and post-therapy. Imaging technologies are the methods of choice in the standard of care to monitor therapy response and disease status in MBC patients. These methods are expensive, time-consuming and have limited sensitivity for real time monitoring. Measurements of circulating tumor markers CA15-3, CA125 and CEA have contributed, albeit with limitation, minimally invasive methods for MBC disease management. It is our hypothesis that measuring biomarkers involved in tumor biological processes may provide better evaluation of the disease state and thus aid real-time clinical management of MBC patients. Thus, addition of such new circulating disease biomarkers may improve the management of MBC patients. The 88kDa glycoprotein Progranulin (GP88/PGRN) fit these criteria. GP88/PGRN is expressed in tumor tissue and not in normal mammary tissue counterpart and secreted in the circulation of BC patients. Biological studies have established GP88/PGRN as a critical driver of BC cell proliferation, survival, invasiveness and drug resistance. Clinical studies have demonstrated that high tumor GP88/PGRN expression was prognostic for recurrence and that breast cancer patients had a statistically elevated GP88/PGRN serum level compared to healthy individuals. In the present study, we examined whether GP88/PGRN serum levels were elevated in MBC patients and whether GP88/PGRN circulating levels were correlated with patient clinical outcome and overall survival.

Under an IRB approved protocol at the University of Maryland Greenebaum Comprehensive Cancer Center, 101 stage 4 BC patients undergoing standard of care therapy and meeting the inclusion criteria were consented and enrolled. MBC patients' demographics, clinical and disease characteristics and therapies were collected as part of the study. Blood samples were collected from each patient at specific times at follow-up visits during and post-therapy. The prepared serum was stored at -80C until tested for GP88 using a GP88 enzyme linked immunoassay developed in our laboratory.

Statistical analysis using Kaplan-Meier functions established whether there was a correlation between GP88/PGRN serum level and overall survival in MBC patients. MBC patients with distinct survival characteristics (P=0.0002) could be stratified based on their circulating GP88/PGRN levels. Analysis of this association was carried out in MBC patients based on their age, race, tumor characteristics, receptor status and metastatic burden (number and sites of metastasis) and will be reported. We conclude that circulating levels of GP88/PGRN in MBC patients are correlated with overall survival and that monitoring circulating GP88/PGRN levels would provide additional information and valuable insight into real-time MBC disease status.

This work was supported by grant R43 CA 210817-01A1 to GS.

Citation Format: Serrero G, Hawkins D, Hicks D, Rosenblatt P, Tait N, Yue B, Tkaczuk K. Circulating level of GP88/Progranulin is associated with clinical outcome and overall survival in stage 4 breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-02-10.