Abstract 5532: Serum progranulin (GP88) level correlates with change in RECIST and survival in metastatic breast cancer
Authors: Serrero Ginette , Hicks David , Hawkins Douglas , Yue Binbin , Rosenblatt Paula , Tait Nancy , Tkaczuk Katherine 
Published: August 2018

Abstract
Monitoring of disease status in metastatic breast cancer (MBC) patients is a necessary step for optimal clinical management of patients during and post-therapy. While imaging technologies are the methods of choice in the standard of care (SOC), they are expensive, time-consuming, and have limited sensitivity. Measurements of circulating tumor markers CA15-3, CA125 and CEA have provided, albeit with limitation, minimally invasive methods for MBC disease management. An ideal approach would be to measure biomarkers involved in tumor biological processes, as they may provide better evaluation of the disease state and thus aid in real-time clinical 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 is secreted into 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 BC 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 serum levels were correlated to patient survival and to a change in disease status as measured by RECIST 1.1.
An IRB approved protocol at the University of Maryland Greenebaum Comprehensive Cancer Center consented and enrolled 101 stage 4 BC patients undergoing SOC therapy. Patient demographics, together with clinical and disease characteristics by RECIST were collected. Blood samples were collected from each patient at follow-up visits during and post-therapy and tested for GP88 using A&G's GP88 enzyme linked immunoassay.
Statistical analyses established a GP88 cut-off value associated with overall survival as well as determined that GP88 level was associated with disease status measured by RECIST criteria. Kaplan-Meier functions established a correlation between GP88 serum level and overall survival in MBC patients that was independent from age, race, tumor characteristics, receptor status and metastatic burden (number and sites of metastasis). Additionally, we examined the data to investigate if change in GP88 serum levels correlated with a contemporaneous change (Progression vs Response) in RECIST/ Clinical findings. Statistical analysis determined that contemporaneous GP88 is significantly associated with disease progression (p=0.0101) and response (p=0.0194).
We conclude that circulating levels of GP88/PGRN in MBC patients are correlated with overall survival and disease status and that monitoring circulating GP88/PGRN levels would provide additional information and valuable insight into real-time MBC disease status.
Citation Format: Ginette Serrero, David Hicks, Douglas Hawkins, Binbin Yue, Paula Rosenblatt, Nancy Tait, Katherine Tkaczuk. Serum progranulin (GP88) level correlates with change in RECIST and survival in metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5532.