Abstract PS5-09-03: Prospective longitudinal study of circulating serum progranulin (PGRN/GP88) levels and its association with tumor response to therapies in patients with metastatic breast cancer (MBC)

Abstract The ability to monitor response to therapy and disease progression in patients with metastatic breast cancer (MBC) is a major step in patient management. Sequential imaging remains the method of choice for the assessment of disease status and monitoring of disease response or progression. Serum levels of tumor-associated biomarkers such as CA15-3 and CEA are also measured to follow MBC patients’ disease status. However, it may also be valuable to measure levels of novel biomarkers that have been shown to be overexpressed in breast cancer tumors and play a role in drug resistance and for which therapeutic development is on-going. Progranulin, also called Glycoprotein 88kDa (PGRN/GP88) is an autocrine growth factor overexpressed in several cancers including breast cancer. PGRN plays a significant role in breast tumorigenesis. PGRN/GP88 overexpression in invasive ductal carcinoma (IDC) is associated with malignant phenotype, estrogen (ER) independence, increased proliferation, survival, angiogenesis, and drug resistance. High PGRN/GP88 tumor expression measured by immunohistochemistry in ER receptor positive IDC is an independent prognostic marker associated with increased risk of recurrence and mortality. Clinical studies have demonstrated that serum PGRN levels determined by sandwich enzyme immunoassay are elevated in breast cancer (BC) patients, compared to healthy individuals. In MBC patients, low serum PGRN levels correlate with increased overall survival. Based on these observations, an IRB approved, prospective study was established at the University of Maryland Greenebaum Comprehensive Cancer Center to examine serum PGRN/GP88 levels in association with disease status as measured by RECIST 1.1 criteria in MBC patients receiving standard of care therapies. A total of 103 MBC patients with measurable or evaluable metastatic disease will be consented and enrolled. For inclusion, patients must have been re-staged within 4 weeks of study entry and continue or begin new anticancer therapy. Currently, 50 patients have been enrolled with blood samples collected every 2-3 months or whenever there is a disease event such as clinical or imaging progression. Standard of care (SOC) laboratory assessments and radiographic imaging/staging will be done on study to complement blood collection to measure PGRN/GP88. The samples are stored at -70C until evaluation of PGRN/GP88 using an enzyme linked immunoassay developed by A&G Pharmaceutical. The serum PGRN/GP88 levels will then be correlated with disease response by RECIST 1.1 (progression, stable for < 6 vs >=6 months, partial/complete response), progression free survival (PFS), duration of response (DOR) and/or need for change of therapy. In this study the decision about the change of cancer therapy will be based on the SOC approaches and will not be guided by PGRN/GP88 results. This study is supported by grant R44CA210817 from the National Cancer Institute to Ginette Serrero and the University of Maryland Greenebaum Comprehensive Greenebaum Cancer Center. Citation Format: K. H. Tkaczuk, K. Hu, P. Y. Rosenblatt, N. Tait, Y. BinBin, G. Serrero. Prospective longitudinal study of circulating serum progranulin (PGRN/GP88) levels and its association with tumor response to therapies in patients with metastatic breast cancer (MBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-09-03.