Abstract PS4-29: Determination of serum progranulin (GP88) levels complements CA15-3 to monitor disease progression & response to therapy in metastatic breast cancer patients

Abstract

Abstract Background: Progranulin (GP88) is a critical player in breast tumorigenesis. High PGRN/GP88 tumor expression measured by immunohistochemistry is associated with increased risk of recurrence and mortality in estrogen receptor positive breast cancer patients. PGRN/GP88 circulating levels are elevated in breast cancer patients, compared to healthy individuals. In the present study, we examined the possible correlation between serum PGRN/GP88 levels in metastatic breast cancer (MBC) patients with overall survival and disease status determined as response to therapy or progression of disease. Methods: An institutional review board (IRB) approved study prospectively enrolled 101 MBC patients at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC). Blood samples were collected during follow-up visits. PGRN/GP88 serum levels were determined by PGRN/GP88 sandwich enzyme immunoassay developed in our laboratory and clinically validated. The serum levels were correlated with patients’ disease status determined by RECIST 1.1 criteria and with survival outcomes by Kaplan Meier analysis and Logrank statistics. Results: Patients’ survival was stratified by serum PGRN/GP88 level. Patients with serum PGRN/GP88 <56 ng/ml had a four-fold increased survival compared to patients with serum levels > 56 ng/ml. Examination of PGRN/GP88 serum levels in association with disease status showed a statistically significant association between serum GP88 levels disease progression or response to therapy. Cox proportional modeling showed that the association of serum GP88 level with survival was independent of age, race and tumor characteristics (ER/PR/Her-2 status, tumor size and lymph node status). We examined the association of serum PGRN/GP88 levels with response to therapy or progression of disease and compared the results with the ones obtained for CA15-3. While serum CA15-3 was strongly associated with progression of disease but not with response to therapy, serum PGRN/GP88 measurements were statistically associated not only with progression of disease but more importantly with response to therapy. Moreover, the information provided by GP88 on disease status (progression or response to therapy) was additive to the one provided by CA15-3 in this study population. Conclusions: The association of serum Progranulin/GP88 level with disease status and its additive value to CA15-3 measurements suggests the potential of using serum progranulin test for monitoring disease status in MBC patients during and post-treatment. Measurement of serum PGRN/GP88 levels in MBC patients will have clinical value as a cost-effective adjunctive to imaging MBC patient management and complementary to CA15-3 determinations. This test can fulfill needs for new and improved tumor biomarkers to monitor disease status and manage risk for patients with metastatic breast cancer. Support: This work was supported by grant 2R44CA210817 from the National Cancer Institute to Ginette Serrero. Citation Format: Ginette Serrero, Katherine R Tkaczuk, Douglas Hawkins, Nancy Tait, Binbin Yue. Determination of serum progranulin (GP88) levels complements CA15-3 to monitor disease progression & response to therapy in metastatic breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-29.