A Circulating Biomarker for use in Monitoring Metastatic Breast Cancer

Period of Performance: 03/15/2017 - 03/14/2018


Phase 1 SBIR

Recipient Firm

A and G Pharmaceutical, Inc.
Principal Investigator


Significance: Despite decreases in the overall number of new breast cancer (BC) cases reported in the US annually, there are still about 40,000 BC deaths annually, ~80% from metastatic breast cancer (MBC). Thus the ability to monitor MBC is important to determine disease status and therapy response. While the gold standard, imaging is expensive, time consuming and slow to detect disease response or progression, circulating biomarkers such as CA15-3, CA27.29 and CEA, also used to monitor MBC have limitations due to low specificity and sensitivity. Thus, providing better safe, inexpensive, non-invasive, specific and sensitive tests for new biomarkers to monitor disease is a key component in improving MBC patient care. Strategy: Measurement of critical biological drivers as biomarkers of the disease will provide a clearer understanding of current disease state and improve proactive clinical management. The PI has characterized a proprietary target biomarker, GP88 expressed in BC tissue, secreted in BC patients? blood and playing a key role in BC tumorigenesis. GP88 IHC and EIA tests to measure GP88 tumor expression and circulating levels in BC patients were developed and clinically validated. Supporting Evidence: Pathological studies have established GP88 tumor expression as a predictive marker for recurrence. Clinical studies have shown BC patients with progressive disease have elevated GP88 serum levels compared to patients with no evidence of disease or healthy individuals. Patients with poor outcome had a significantly higher GP88 serum levels (56ng/ml, range 40-146ng/ml) than alive patients (36ng/ml, range 30-46ng/ml), p=0.016. These data indicate that if GP88 blood levels are maintained below a yet to be established cut-off level, then a patient can be expected to have a longer survival than patients with elevated GP88. Hypothesis: Measuring serum GP88 level could provide an ideal approach for monitoring disease status in MBC patients as adjunctive to imaging. This hypothesis will be investigated by measuring GP88 levels in sequential retrospective serum samples collected from 140 MBC patients enrolled in an IRB approved study at UMGCCC and correlate such levels with objective measures of clinical outcome determined using RECIST 1.1 criteria. Specific Aims: we will: 1a) establish by Kaplan-Meier survival graphs a GP88 threshold value that stratify BC patients for survival and clinical outcomes; 1b) determine if changes in GP88 serum level correlate with changes in RECIST1.1 criteria collected at the same time-points; 2) using receiver operating characteristics curves, identify GP88 cutoff values that effectively stratify patients by their clinical outcome; 3) using multivariate analysis and logistic regression evaluate if combining GP88 and CA15-3 results can improve upon, and enhance, the predictive performance of CA15-3. Overall Impact: Since GP88 is a driver of the disease, the use of the GP88 EIA test has the potential to provide real-time evaluation of the disease state, making GP88 a better biomarker to monitor MBC than those currently available. This will provide clinicians with a new assay to assess disease status to increase predictive values of existing techniques such as imaging.