Abstract P1-02-12: Determination of a serum progranulin (GP88/PGRN) level associated with overall survival in metastatic breast cancer patients
Authors: Serrero G , Hawkins DM , Yue B , Hicks D , Tait N , Tkaczuk KR 
Published: March 2017

Imaging technologies are the methods of choice in the standard of care (SOC) to monitor therapy response in metastatic breast cancer (MBC) patients. However, such methods are expensive and have limited sensitivity to detect disease response in a timely manner. Measurement of the circulating tumor markers such as CA15-3, CA27.29 and CEA has provided additional minimally invasive methods in disease management of MBC patients. While useful, they have limitations in providing clinicians with a reliable insight into real-time disease monitoring. Understanding of real-time biological processes may provide better biomarkers of the disease state and thus aid real-time clinical management of MBC patients by identifying circulating disease associated biomarkers. Thus, addition of such new circulating biomarkers may improve the management of MBC patients. We have characterized a target biomarker that would fit these criteria, the 88kDa glycoprotein Progranulin (GP88). GP88 is expressed in tumor tissue and not in normal mammary tissue counterpart and is secreted in the circulation of BC patients. Biological studies have established GP88 as one of the critical drivers for breast cancer cell proliferation, survival, invasiveness and drug resistance. Clinical studies have demonstrated that elevated GP88 tumor levels were prognostic for recurrence and that breast cancer patients had a statistically elevated GP88 serum level than healthy individuals. Using tissue and serum tests to detect and quantify GP88 could provide an new strategies for identifying patients at high risk of recurrence and monitoring disease progression in BC patients undergoing therapy. In the present study, we examined whether GP88 serum levels were elevated in MBC patients and whether GP88 serum levels were correlated to patient overall survival.

Under an IRB approved protocol, 92 MBC patients that met the inclusion criteria and were undergoing therapy at the UMGCCC Breast Clinic were consented and enrolled. Clinical and disease characteristics along with serum CA15-3 values were collected as part of the study. Serum samples were collected from each patient during therapy and subsequently the patients were monitored. The 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 serum level and overall survival in MBC patients. By analyzing the KM plots at different GP88 cut points, we identified two populations with distinct survival characteristics. When examined more thoroughly the difference in overall survival of patients with &lt;60ng/ml and &gt;60ng/ml was statistically significant (P=0.0002). Correlation analysis of serum GP88 and CA15-3 were performed and will be presented.

We conclude that circulating levels of GP88 in MBC patients are correlated with overall survival. It would appear that patients that can be managed to have a GP88 below 60ng/ml will survive longer. Thus measuring circulating GP88 levels would provide additional information to that available in today's SOC for monitoring. This valuable insight into real-time disease status will assist clinicians in patient management.

Citation Format: Serrero G, Hawkins DM, Yue B, Hicks D, Tait N, Tkaczuk KR. Determination of a serum progranulin (GP88/PGRN) level associated with overall survival in metastatic breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-12.