Prof. Barbara Burwinkel, DKFZ / University Clinic Heidelberg
Conventional tumor markers have limited value for prognostication and treatment monitoring in metastatic breast cancer (MBC) patients and novel circulating tumor markers therefore need to be explored. Hyaluronic acid (HA) is a major macropolysaccharide in the extracellular matrix and is reported to be associated with tumor progression. In our study, we investigated plasma HA level with respect to progression free survival (PFS) and overall survival (OS), as well as the treatment monitoring value in MBC patients. The prognostic value of plasma HA level was investigated in a discovery cohort of 212 MBC patients with 2.5-year follow-up and validated in an independent validation cohort of 334 patients with 5-year follow-up. The treatment monitoring value of plasma HA level was investigated in 61 MBC patients from discovery cohort who had been radiographically examined after first complete cycle of chemo therapy. We found a robust association between high plasma HA level and poor prognosis of MBC patients in both discovery (pPFS = 7.92 × 10(-6) and pOS = 5.27 × 10(-5)) and validation studies (pPFS = 3.66 × 10(-4) and pOS = 1.43 × 10(-4)). In the discovery cohort, the plasma HA level displayed independent prognostic value after adjusted for age and clinicopathological factors, with respect to PFS and OS. Further, the decrease of plasma HA level displayed good concordance with treatment response evaluated by radiographic examination (AUC = 0.79). Plasma HA level displays prognostic value, as well as treatment monitoring value for MBC patients.
The technology describe two serum/plasma markers, in combination or alone, for stage discrimination and prediction of survival as well as treatment response in breast cancer patients. Test statistics show that these markers perform better than established ones like the number of circulating tumor cells (CTCs).
DKFZ is looking for a commercial partner to establish the test (Plasma S100P and hyaluronic acid) for metastatic breast cancer in a routine clinical setting.
Marker approved and verified in studies of 320 (S100P in combination with HA) and 334 (HA only) patients with different disease stages.
Priority patent application filed April 16th in 2014 “New Biomarkers for metastatic breast cancer” as EP 1416486 5.9. PCT filed as WO2015/158652, which was nationalized in Europe (EP3132266, pending), China (CN106489074, pending) and USA (US2017030912, pending).
(1) S100P and HYAL2 as prognostic markers for patients with triple-negative breast cancer. Maierthaler M. et al. Exp Mol Pathol. 2015 Aug;99(1):180-7, see https://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+26112095
(2) Plasma Hyaluronic Acid level as a Prognostic and Monitoring Marker of Metastatic Breast Cancer. Peng et al. Int J Cancer. 2015 Dec 19, see https://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+26686298