Abstract OT1-05-01: Glycoprotein 88 (GP-88) serum levels as a marker of response to therapy in patients with metastatic breast cancer

Abstract

Abstract The ability to detect metastatic breast cancer (MBC) & readily monitor response to therapy is an important goal in the management of breast cancer (BC). Imaging is used for the assessment & monitoring of disease progression. However, this is expensive & represents a late marker of disease status. The disease may progress significantly on ineffective treatment & the patient may have treatment related toxicities due to the lack of knowledge of the progression at earlier times. Circulating tumor associated biomarkers CA15-3 & CEA can be used to track disease status of MBC, however, they are not always a reliable measure of disease progression. The monitoring of disease progression through measurement of drivers of disease may better reflect the disease status & enable proactive management sooner. GP88 (granulin/epithelin precursor or progranulin) has been identified as a driver of tumorigenesis & disease progression through its signaling as an autocrine growth & survival factor for several cancers including BC1. We hypothesized that measurement of circulating serum GP88 levels can serve as a biomarker to monitor MBC disease status & be prognostic to outcome 2. Clinical studies have demonstrated circulating levels of GP88 statistically differ in healthy volunteers, early BC patients (pts), & pts with metastatic disease & levels correlate with overall survival2,3. The primary aim of this prospective study is to identify whether there is a statistically significant change in serum GP88 levels associated with response to treatment & time to progression of BC as measured by RECIST 1.1 criteria in MBC pts. Under an IRB approved protocol at the University of Maryland Greenbaum Comprehensive Cancer Center, a total of 103 female pts with measurable or evaluable metastatic disease who have been re-staged in within 4 weeks & will continue or begin new therapy & meet the additional criteria will be consented & enrolled. Currently, we have enrolled 23 pts. In addition to standard of care laboratory assessment & radiographic imaging/staging every 2-3 months, blood samples will be collected from each patient. The samples will be stored at -70C until tested for GP88 using a GP88 enzyme linked immunoassay. We will analyze the serial GP88 serum levels & correlate with treatment response using RECIST 1.1 criteria (stable, progression, response), time to progression & overall survival. We assume that pts will provide a baseline & 4 follow up visits/GP-88 levels & that 20% of the visits will record a disease progression & time to progression. The probable & clinically relevant GP-88 test performance will then have 75% sensitivity & 46% false positivity with 85% power in a sample of 90 pts.