Cost-effective and minimally invasive monitoring of metastatic breast cancer (MBC) patients for disease progression or response to therapy is an unmet need in the clinical management of the disease. Imaging technologies are currently the gold standard of such monitoring. However, there is controversy regarding the type & frequency of imaging required. Imaging is expensive, time consuming, slow to detect disease changes and raises concern about repeated radiation exposure and costs are not always covered by insurance. Complementary approaches to imaging such as circulating tumor cells and biomarkers are used in the Standard of Care (SOC), although their application remains limited. A simple, cost-effective blood test to measure the level of biomarkers which are drivers of the disease aggressiveness should provide novel solutions for real-time monitoring of therapy response and reduce dependency on imaging in the MBC population. The PI has identified an 88kDa glycoprotein GP88 (progranulin), elucidated its biological activity as an autocrine growth & survival factor. GP88 is secreted from cancer cells and measurable in biological fluids at higher levels in breast cancer patients, compared to healthy individuals. Based on these characteristics, an innovative diagnostic test (Enzyme Immunoassay ? EIA) to measure GP88 in circulation was established. Our SBIR Phase 1 retrospective study demonstrated a statistical association between serum GP88 levels measured by the EIA test and objective measures of disease, i.e. RECIST 1.1 in 101 MBC patients. We established that a serum GP88 level of 56ng/mL was a stratification point below which patients have improved overall survival while patients with GP88>56 ng/ml have a poor outcome. We showed that serum GP88 levels were statistically correlated to response to therapy in addition to progression of disease unlike the SOC biomarker CA15-3 which is only associated to progression of disease. Based on these promising data, we are proposing an SBIR Phase 2 prospective longitudinal study over a 15-month period enrolling 120 MBC patients at two clinical sites by measuring serum GP88 level every month with imaging performed every 3 months. The objectives are to validate the findings of phase 1 and establish the predictive use of the GP88 test in monitoring MBC patients for disease progression/ response as an adjunct to imaging and aid in the clinical management of such patients. Specifically, we will (1) Validate that serum GP88 levels are correlated to disease response/ progression as defined by imaging results; (2) Examine the impact of successive high (>56ng/mL) and low (<56ng/mL) GP88 blood levels on future response/ progression and time to progression as defined by imaging results; (3) Validate that patients with consistent low (<56ng/mL) GP88 blood levels, have improved survival compared with patients with consistently high (>56ng/mL) GP88 blood levels. The outcomes of this phase 2 will be to establish clinical data to support commercialization of GP88 EIA as an integral part of clinical management of MBC patients that will contribute to improved care of MBC patients at reduced cost.
There are ~40,000 deaths each year attributed to breast cancer of which 30,000 are as a result of metastatic cancer. The ability to detect disease progression is important in the overall management of metastatic breast cancer patients. While imaging remains the gold standard for monitoring disease status, it is expensive, time consuming, slow to detect disease response or progression and there is concern about repeated exposure to the associated radiation. Alternative approaches complementary to imaging have been considered or introduced in the practice although their application in the Standard of Care remains limited. Monitoring of disease status could be vastly improved by the measurement of biological markers involved in the disease process. We have demonstrated that blood levels of such a biomarker, GP88, are correlated with objective measures of disease status. In this Phase 2 grant application, we are proposing a longitudinal study to enroll 120 metastatic breast cancer patients to examine prospectively the ability of the GP88 blood test to monitor disease status and predict response to therapy or progression of the disease in real time. If we are successful, we will provide to the patients and their treating oncologists a novel solution for patient monitoring in the form of a simple cost-effective and minimally invasive blood test to predict changes in disease status ahead of restaging by imaging. This alone will be a significant step in the clinical management of MBC patients by providing information on the patients? disease status resulting in lowering exposure to radiation, decreasing toxicities of unnecessary drugs and improving quality of life for MBC patients.
