Elevated preoperative serum levels of collagen I carboxyterminal telopeptide predict better outcome in early-stage luminal-B-like (HER2-negative) and triple-negative subtypes of breast cancer

• Main Authors: Anniina Jääskeläinen, Arja Jukkola, Juha Risteli, Kirsi-Maria Haapasaari, Peeter Karihtala
• Format: Article
• Language: English
• Published: IOS Press 2019-05-01
• Series: Tumor Biology
• Online Access: https://doi.org/10.1177/1010428319847081

Type 1 collagen is an important part of the extracellular matrix and changes in its metabolism and distribution are essential in breast cancer induction and progression. Serum concentrations of type 1 collagen synthesis (aminoterminal propeptide (PINP)) and degradation markers (carboxyterminal telopeptide (ICTP)) have previously been studied in early and metastatic breast cancer, but no data are available on specific breast cancer subtypes. We assayed 662 preoperative serum samples for PINP and ICTP and 109 postoperative serum samples for ICTP. The results were linked to prospectively collected clinical data and the cases were divided into breast cancer subtypes for survival analyses. The concentrations of both pre- and postoperative ICTP serum levels increased linearly from ductal in situ carcinoma to stage I–II tumors, stage III tumors, and finally to those with concomitant primary metastases (preoperative ICTP, p = 0.009; postoperative ICTP, p = 0.016). High-preoperative ICTP levels were associated with better breast cancer-specific survival in connection with luminal-B-like (HER2-negative) tumors (p = 0.017), which was confirmed in Cox regression analysis (relative risk = 3.127; 95% confidence interval = 1.081–9.049, p = 0.035), when T-class (relative risk = 4.049; 95% confidence interval = 1.263–12.981; p = 0.019) and nodal status (relative risk = 3.896; 95% confidence interval = 1.088–13.959; p = 0.037) were included in the analysis. In patients with triple-negative breast cancer, a high-preoperative ICTP level was a significant predictor of local relapse-free survival in univariate (p = 0.0020) and multivariate analyses (relative risk = 13.04; 95% confidence interval = 1.354–125.5; p = 0.026; for T-class, relative risk = 2.128 and 95% confidence interval = 0.297–15.23; p = 0.452; for N-class, relative risk = 0.332 and 95% confidence interval = 0.033–3.307; p = 0.347). A preoperatively elevated serum ICTP level appears to be an important marker of better prognosis in triple-negative breast cancer and luminal-B-like (HER2-negative) subtypes.