Abstract OT3-03-03: A prospective study of glycoprotein 88 (GP-88) blood test in healthy women undergoing screening for breast cancer (BC) with mammography (MM)
Authors: Tkaczuk KHR , Campassi C , Kesmodel S , Bellavance E , Rosenblatt P , Nichols E , Feigenberg SJ , Coughlin P , Drogula C , Urban B , Galandak J , Dromi S , Kuo L , Yue B , Hicks D , Serrero G 
Published: May 2016

Abstract
Background: Population based BC screening with XRAY mammography (MM) has been widely accepted as standard of care for women aged 40+ with average risk of developing BC. Sensitivity and specificity of MM is dependent on breast tissue density and up to ∼20% of BC are undetected by MM. The development of a dependable, low cost blood-based BC screening test to increase the sensitivity and specificity of currently existing BC screening methods is needed.
Rationale: GP88 is expressed & secreted by BC cells & is not expressed by normal mammary epithelial cells, 2 retrospective randomized multi-site trials (a training study & a validation study of 300 cases each) demonstrated that elevated GP88 expression in estrogen positive (ER+) invasive BC was statistically correlated with a 4-fold increase in the risk of 5-yr BC recurrence. GP88 was an independent predictor of BC recurrence in multivariate analysis of other factors such as PR expression, tumor size, grade, lymph node status & stage. The quantitative GP88 EIA was developed to determine the amount of GP88 in biological fluids. The blood based EIA assay is highly specific for GP88 & both sensitive & linear over a wide dynamic range, i.e. detection of GP88 concentrations from 0.1 to 20ng/ml. A baseline GP-88 level of28.4 ± 5 ng/ml was established by us for healthy volunteers (HV). In BC pts a statistically significant increase of serum GP88 was observed in early stage pts (40.7 ± 16 ng/ml; p=0.007). Stratification of BC pts according to their clinical outcomes shows that pts having no evidence of disease (NED) have serum GP88 levels within the range of HV. These data suggest that pts with breast tumors express & secrete high levels of GP88.
Objectives: 1. To determine prospectively GP-88 blood levels in HV at average risk of developing BC screened by MM & in women with recently biopsy-confirmed BC. 2. To establish the statistical distribution of GP88 serum levels in subjects by baseline BIRAD classification (1-6). 3. To determine if the initial GP88 level is predictive of change in BIRADS classification from baseline to 12-mos follow-up. 4. To determine if baseline GP88 level is predictive of the appearance of BC at 12 mos follow-up in HV who were cancer-free at study entry.
Inclusion Criteria: Female, aged &gt;=40 yrs old, presenting for screening or diagnostic MM or diagnostic workup and/or biopsy due to abnormal MM &lt;= to 12 wks before study entry.
Study procedures: Serum levels of GP88 in subjects with average BC risk factors will be measured prospectively at baseline; 3-6 mos & 6-12 mos & correlated with BIRADS reading of the screening MM, BIRADS 1-6; GP88 serum level will be correlated with pathologic results of breast biopsies performed on subjects with suspicious BIRADS (4 & 5) MM & final pathologically confirmed diagnosis of breast cancer as BIRADS 6.
Study Progress: The study is ongoing; currently we have 308 subjects enrolled, the total number of subjects will be up to 725 & screened up to 1400. Study is UM IRB approved & is conducted at the University od Maryland Medical Center (UMMC) and UM Baltimore Washington Medical Center (BWMC). Funding is provided by Maryland Industry Partnership Grant (MIPS)& Avon Grant No. 02-2013-018.
Citation Format: Tkaczuk KHR, Campassi C, Kesmodel S, Bellavance E, Rosenblatt P, Nichols E, Feigenberg SJ, Coughlin P, Drogula C, Urban B, Galandak J, Dromi S, Kuo L, Yue B, Hicks D, Serrero G. A prospective study of glycoprotein 88 (GP-88) blood test in healthy women undergoing screening for breast cancer (BC) with mammography (MM). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-03-03.