Abstract P5-12-10: Circulating progranulin (GP88) level is associated with both response to therapy and progression of disease in metastatic breast cancer patients

Abstract

Abstract Imaging is the method of choice for monitoring of disease response to therapy during and post-treatment in metastatic breast cancer (MBC) patients. However, imaging has limited sensitivity for real-time monitoring so clinicians use circulating tumor markers such as CA15-3, as surrogates for monitoring changes in disease, albeit with some limitations. Measuring tumor markers associated with the biologically driven tumor processes of development, proliferation and survival would add significantly to current disease information available and would improve the clinical management of this underserved patient population. Biological studies demonstrated that the 88kDa glycoprotein Progranulin (GP88) is a critical driver of breast cancer (BC) cell proliferation, survival, invasiveness and drug resistance. GP88 is expressed in tumor tissue and not in normal breast tissue and is secreted in the circulation of BC patients. Studies demonstrated that high tumor GP88 expression is prognostic for recurrence and that BC patients had a statistically elevated GP88 serum level compared to healthy controls. We hypothesized that changes in serum GP88 levels correlate with changes in disease state as defined by RECIST 1.1. In this current study, we examined whether GP88 and CA15-3 serum levels were correlated to disease progression and response to therapy. Additionally, we compared the information provided by the GP88 /CA15-3 combination in disease progression or response to therapy. 101 stage 4 MBC patients undergoing Standard of Care therapy were consented and enrolled under an IRB approved protocol at the University of Maryland Greenebaum Comprehensive Cancer Center. Patient demographics together with clinical and disease characteristics were collected as part of the study. Blood samples were drawn from each patient at specific times at follow-up visits during and post-therapy and tested for GP88 using A&G's GP88 enzyme linked immunoassay. Samples were tested for CA15-3 at the University's laboratory. Disease status was monitored and assessed by RECIST1.1 criteria and such assessment entered into the database. Statistical analyses were carried out using the serum GP88 and CA15-3 results to test each for association with contemporaneous RECIST assessment of disease progression (PD) or response (R). We determined that contemporaneous GP88 is significantly associated with PD (p 0.0101) and R (p 0.0194) while CA-15-3 is associated with PD (p <0.001) but not R (p 0.7316). Further, we used logistic regression to examine for additional information provided by each biomarker by modelling disease (PD or R) as dependent on the log-transformed GP88 and CA15-3 values. We determined that both GP88 and CA15-3 show significance for PD meaning biomarkers adds information while for R only GP88 had high significance meaning GP88 alone is significant and sufficient for R and CA15-3 does not add any value. We conclude that circulating levels of GP88/PGRN in MBC patients are correlated with both disease progression and response to therapy and that monitoring circulating GP88/PGRN levels would be complementary to CA15-3 determination and imaging to provide valuable insight into real-time monitoring of the disease status of MBC patients. Citation Format: Serrero G, Hawkins DM, Hicks DJ, Tait N, Yue B, Tkaczuk KR. Circulating progranulin (GP88) level is associated with both response to therapy and progression of disease in metastatic breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-12-10.