Type 1 collagen degradation marker ICTP in locally advanced breast cancer response to neoadjuvant chemotherapy.

Abstract

Background: The aim of this pilot study was to evaluate the correlation between response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer and plasma levels of carboxy-terminal cross-linked telopeptide of type 1 collagen (ICTP). ICTP is a degradation product of Type 1 collagen which is one of the major component of extracellular matrix (stroma) of tumours. Degradation of this collagenous matrix by tumour or stromal cell-derived proteolytic activity may facilitate tumour cells or some degraded component into systemic circulation. Alterations in these products may be useful monitoring tumour behaviour and treatment reponse in cancer patients. Material(s) and Method(s): Following informed consent, 21 patients with locally advanced breast cancer suitable for NCT were recruited. Participants were randomly assigned to receive either sequential FEC100(x4) and Docetaxel 100/m2(x4), or the reverse sequence. Serial assessment of response was performed with physical examination, mammography, ultrasound, tumour biopsy and PET scans. Blood samples were collected at baseline, after 4 cycles of chemotherapy and lastly at the time of surgery. Plasma ICTP levels were determined in a blinded way using the UNIQ ICTP RIA assay(Orion Diagnostics, Finland) and compared with final pathological response (complete/partial vs no response). Result(s): Increase in ICTP level was seen in 12/13 patients responding to NCT. Eight patients with poor pathological response had mixed levels with no overall increase in ICTP level. The trend seen did not reach statistical significance. Discussion(s): It is speculated that the rise in ICTP level is in response to ongoing stromal resonse in these patients' tumours and hence increase in matrix metalloproteinase (MMP) activity. This study is limited by small numbers of patients enrolled. Further investigation by gene expression studies is required to confirm these observations and the usefulness of ICTP in monitoring treatment response in breast cancer patients. The current study is ongoing and further results will be reported when they become available.