ASCO Annual Meeting 2017
EXTRACELLULAR MATRIX (ECM) PROTEIN FRAGMENTS IN SERUM AND OUTCOMES IN TWO METASTATIC BREAST CANCER COHORTS
Background: Extracellular matrix (ECM) is the non-cellular component of all tissues. Increased ECM formation and matrix metallo-protease (MMP) mediated ECM degradation are parts of tumorgenesis. The altered ECM remodeling generates specific ECM fragments that are released into the circulation. We evaluated the association of specific ECM/collagen fragments measured in serum with outcomes in two independent metastatic breast cancer (MBC) cohorts. Methods: C1M (MMP-degraded type I collagen), C3M (MMP-degraded type III collagen), C4M (MMP-degraded type IV collagen), and PRO-C3 (pro-peptide reflecting truetype III collagen formation) were measured by ELISA in pre-treatment serum from a phase III randomized clinical trial of 2nd-line hormone therapy (HR+, n= 153), and a 1st-line trastuzumab-treated cohort (HER2+, n=64). In both cohorts, all sites of metastases were included. The collagen-fragments were evaluated on continuous and categorical (75th percentile cut-off) bases by univariate Cox-regression analysis for their association with time-to-progression (TTP) and overall survival (OS). Results: In the HR+ cohort, Pro-C3 measured as a continuous variable was significantly associated with TTP; C1M, C4M and Pro-C3 were associated with OS. On a categorical basis, C1M and C3M were associated with TTP; all fragments were associated with OS (Table). In the HER2+ cohort, continuous measurements of all fragments were associated with TTP and OS. On a categorical basis (Table), all fragments were associated with TTP; C4M and Pro-C3 were associated with OS. Conclusions: ECM remodeling quantified in pre-treatment serum was associated with shorter TTP and OS in two independent MBC cohorts receiving systemic therapy. If validated, quantification of ECM remodeling in serum has potential as prognostic and/or predictive biomarkers in MBC.
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