Abstract OT3-16-01: On-going prospective study to measure serum progranulin/GP88 levels in metastatic breast cancer patients in association with disease status

Abstract The ability to monitor response to therapy and disease progression in metastatic breast cancer (MBC) patients is a major step in patient management. Imaging is the method of choice for the assessment of disease status and the monitoring of disease progression. However, this approach remains expensive, expose patients to radiation and thus is mainly performed every 2-3 months. During this time interval, the disease may progress significantly on ineffective treatment and the patient may present treatment related toxicities due to the inability to detect progression at earlier times. Circulating levels of tumor associated biomarkers such as CA15-3 and CEA are often determined to track disease status of MBC. However, even though they can provide information about disease progression, they do not always provide a reliable measure of response to therapy. The monitoring of disease status and progression through the measurement of drivers of disease should provide an alternative and complementary approach to existing strategies in order to better to monitor the disease status and enable proactive management of MBC patients. Progranulin also called Glycoprotein 88kDa (PGRN/GP88) is an autocrine growth factor overexpressed in breast cancer. Biological studies have established GP88 as a critical player in breast tumorigenesis. GP88 overexpression is associated with the malignant phenotype, estrogen independence, increased proliferation, survival, and drug resistance. High PGRN/GP88 tumor expression measured by immunohistochemistry in invasive ductal carcinoma is an independent prognostic marker associated with increased risk of recurrence and mortality. Clinical studies have demonstrated that GP88 circulating levels as measured by enzyme immunoassay are elevated in breast cancer patients, compared to healthy individuals. In MBC patients, circulating GP88 levels correlate with overall survival. These facts are supportive of the hypothesis that the measurement of circulating GP88 levels in MBC patients can serve as an additional biomarker to monitor MBC disease status and be predictive to outcome. A prospective study was established is to identify whether there is a statistically significant change in serum GP88 levels associated with time to progression of breast cancer as measured by RECIST 1.1 criteria in MBC patients. With the assumptions that patients will provide a baseline and four follow up visits and that 20% of the visits record a disease progression, time to progression. Taking the plausible and clinically relevant performance to be 75% sensitivity and 46% false positive, a sample of ninety patients would give 85% power. Under IRB approved protocols at the University of Maryland Greenebaum Comprehensive Cancer Center and at two Baltimore Medstar Health Facilities, a total of 103 female breast cancer patients with measurable or evaluable metastatic disease will be consented and enrolled. The patients have been re-staged within 4 weeks and will continue or begin new therapy. Currently, we have enrolled sixty-five subjects at the three facilities. In addition to standard laboratory assessment and radiographic imaging/staging every 2-3 months on study, blood samples will be collected from each patient. The samples are stored at -70C until evaluated for GP88 using a GP88 enzyme linked immunoassay. We will analyze the GP88 serum level in correlation with survival and with disease status determined as responder, stable or progressing based on the RECIST criteria. This study is supported by grant R44CA210817 from the National Cancer Institute to Ginette Serrero Principal Investigator. Citation Format: Ginette Serrero, Paula Rosenblatt, Nancy Tait, Barbara Rector, Jennifer A. Latteri, Binbin Yue, Katherine Tkaczuk. On-going prospective study to measure serum progranulin/GP88 levels in metastatic breast cancer patients in association with disease status [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-16-01.