Plasma angiogenic markers in patients with metastatic breast cancer treated with weekly docetaxel.

Abstract

e21004 Background: The aim of the study was to evaluate angiogenic plasma markers in patients with metastatic breast cancer (MBC) treated with first-line weekly docetaxel (D), considered to be standard treatment at the time of the design of the study. Methods: Females with MBC were treated with weekly D 35 mg/m2 ± trastuzumab. Plasma levels of HER2 extracellular domain (HER2-ECD), nitric oxide (NO), interleukin-8, and VEGF-A were measured by ELISA before and after the treatment, as well as in 38 healthy female controls. Prognostic and predictive significance of the pre-treatment values and their relative change with treatment were tested by Cox-regression analysis. Results: Between February 2006 and January 2008, 159 patients were treated. 61 patients (38%) responded (CR = 5%, PR = 33%) and 52 (33%) had stable disease. 37 patients received trastuzumab. Median follow-up was 33 months (2.8-45.0), median PFS 8.8 months (95%CI: 7.2-10.3) and median survival 27.7 months (95%CI: 24.7-30.6). HER2-ECD was the only plasma marker that decreased significantly with treatment (p < 0.001), from 2.08 ng/mL (range 0.2- 13.12) to 1.4 ng/mL (range 0.1-12.72). Normal controls had significantly higher NO levels than that of MBC patients before treatment (282.5 vs 199 umol/L, respectively; p = 0.006), whereas HER2-ECD levels were marginally lower (1.76 vs 2.08 ng/mL, respectively; p = 0.054). High pretreatment HER2-ECD levels were of adverse prognostic significance for survival and PFS (p = 0.033 and p = 0.046, respectively) in patients not treated with trastuzumab. High pretreatment NO levels were also of adverse prognostic value (p < 0.001 for survival, p = 0.004 for PFS), as were high pre-treatment IL8 values (p = 0.048 for survival). Plasma VEGF-A did not appear to have prognostic value. High NO relative change was associated with better survival (p = 0.003), in contrast patients with high IL8 relative change were found to have a worse PFS (p = 0.017). Responders had a smaller relative change of IL8 (p = 0.038) than non- responders. Conclusions: HER2-ECD, NO and IL8 plasma levels appear to be of prognostic value for survival in patients with MBC treated with weekly docetaxel. Tumor angiogenic markers will also be examined by PCR in these patients. No significant financial relationships to disclose.