Bevacizumab changes in patients with naïve, stage II-III breast cancer assessed by 18F-fluoromisonidazole and 18F-fluorotymidine PET-CT.

Abstract

2529 Background: PET offers a non invasive tool to assess cancer biology, staging tumors and potentially monitoring treatment response, anti-angiogenic therapy included. The aim of this study was to evaluate the effects of bevacizumab in breast cancer (BC) patients (pts) by fluoromisonidazole (MISO) and Fluorotymidine (FLT) PET imaging as indicators of hypoxia and proliferation rate. Methods: 73 pts (49 yr, range 29-70) with biopsy-proven BC were prospectively enrolled. Pts received one infusion of bevacizumab (15 mg/ kg) (C1) 3 weeks prior to the beginning of chemotherapy consisting in 4 cycles of docetaxel (60 mg/mq), adriamicine (50 mg/mq) and bevacizumab (15 mg/ kg) every 21 days (C2-C5). All pts had MISO and FLT studies and paired tumor-biopsies pre and post C1. MISO and FLT uptakes were correlated with immunohystochemic (IHC) biomarkers. Association between SUVmax values and clinic-pathological characteristics was analyzed using Kruskal-Wallis and Mann-Whitney tests. To compare paired SUVmax values and to test correlation with IHC expression Wilcoxon and Spearman rank test were used. Results: Median baseline MISO and FLT values in tumors were 1.2 (range 0.69-2.39) and 2.89 (range 0.97-7.18). FLT and MISO uptakes were significantly higher in IIIA stage versus IIA-IIB (3.9 vs 2.6) and (1.45 vs 1.19) and in estrogen (ER) negative versus positive tumors (3.7 vs 2.6) and (1.09 vs 1.59). Significant change after one bevacizumab administration was observed in FLT (2.7 vs 1.8, p<0.001) but no in MISO uptake. FLT was correlated with Ki67 index and MISO with VEGFR2-IHC expression (r2=0.336 and r2=0.314, p<0.01). Conclusions: Bevacizumab determines a marked decrease in tumor proliferation rate. Hypoxic status in BC was high, associated with VEGFR2 overexpression, but, interestingly, no change after bevacizumab. These findings have direct implications in understanding bevacizumab effects in breast cancer biology. PET studies seem to be novel pharmacodynamic biomarkers able to distinguish antivascular from antitumor effects of antiangiogenic agents. In the future, their role as potential predictive biomarkers will be investigated.