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.

 

Biomarker HR+ MBC
HER2+ MBC
HR 95% CI p-value HR 95% CI p-value
TTP
C1M 1.59 1.04-2.42 0.032 3.07 1.52-6.18 0.002
C3M 1.51 0.99-2.29 0.056 2.63 1.29-5.35 0.008
C4M     ns 1.96 1.03-3.73 0.041
Pro-C3     ns 1.95 1.02-3.72 0.042
OS
C1M 2.34 1.52-3.59 <0.0001     ns
C3M 1.64 1.04-2.55 0.03     ns
C4M 1.75 1.11-2.73 0.015 1.89 0.95-3.74 0.069
Pro-C3 1.95 1.22-3.09 0.005 3.37 1.67-6.80 0.001