Clinical relevance of collagen protein degradation markers C3 M and C4 M in the serum of breast cancer patients treated with neoadjuvant therapy in the GeparQuinto trial

Background:

Remodeling of extracellular matrix through collagen degradation is a crucial step in the metastatic cascade. The aim of this study was to evaluate the potential clinical relevance of serum collagen degradation markers (CDM) C3 M and C4 M during neoadjuvant chemotherapy for breast cancer.

Methods:

In the GeparQuinto phase 3 trial, patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7, 2007, and July 9, 2010 and randomly assigned to receive neoadjuvant treatment with EC/docetaxel with either trastuzumab or lapatinib. Blood samples were collected at baseline, after 4 cycles and at surgery. Cutoff values were determined using the Cutoff Finder Charite (Budczies et al. PLoS ONE 2012), (C3 M: low ≤9.00 ng/ml, high > 9.00 ng/ml, C4 M: low ≤40.91 ng/ml, high > 40.91 ng/ml).

Results:

128 patients were included in this analysis. At baseline, 11.7% and 14.8% of patients had high C3 M and C4 M serum levels, respectively. No correlation was observed between CDM and classical clinical-pathological factors. Patients with high levels were significantly more likely to achieve pCR. Median levels of both markers were lower at time of surgery than at baseline. In the entire cohort, elevated C4 M levels at baseline significantly predicted shorter DFS but not OS, while high C3 M levels were significantly associated with DFS and OS only in patients receiving lapatinib in the univariate analysis.

Conclusions:

Collagen degradation markers are associated with response to neoadjuvant therapy and seem to play a role in breast cancer.

Trial registration:

NCT00567554.