Imaging early changes in proliferation during Bevacizumab therapy in locally advanced breast cancer with 18F-FLT PET/CT

Objectives To investigate the effect of Bevacizumab on tumor proliferation by assessment metabolic changes with 18F-FLT PET/CT in patients with locally advanced breast cancer (Imaging Clinical Trial).

Methods Forty-six untreated patients with locally advanced breast cancer underwent 18F-FLT PET/CT before and after a dose of Bevacizumab. Uptake of 18F-FLT in tumor was analyzed visually and the maximum SUV was calculated. Tumor biopsies were obtained before and after treatment. The association of 18F-FLT uptake with clinicopathologic characteristics and with Ki-67 proliferation index was studied.

Results 18F-FLT uptake was visualized in 43 (93%) tumors. An association of baseline SUV values with histopathological tumor grading (G1-G2=2.2, G3-G4=3.6;p=0.03), clinical stage (II vs III, 2.6 vs 4.3, p<0.01) and estrogen receptors (ER) status (ER+ vs ER− 2.6 vs 3.5, p=0.08) was observed. Mean SUV in the primary tumors before and after Bevacizumab were significantly different (3.1±1.6 vs 2.2±1.5, p<0.01) with a >30% decrease in 20 patients. The change of 18F-FLT SUV after bevacizumab correlated with the change of the Ki-67 index (rho=0.33;p=0.03). In 14 patients, the axillary lymph node status was also evaluated and showed a positive uptake (mean SUV 3.3±1.7). After treatment the nodal uptake decreased significantly (SUV 2.3±1.6, p<0.01) with a >30% decrease in 6 patients.

Conclusions 18F-FLT showed an excellent sensitivity to detect breast cancer and was associated with important clinicopathologic characteristics such as tumor grade, hormonal status and clinical stage. An anti-proliferative effect of Bevacizumab in both tumors and lymph node metastasis was observed. The change of FLT correlated with the change of Ki-67 index confirming the 18F-FLT PET imaging as a proliferation biomarker. 18F-FLT appears to be a promising tracer of bevacizumab response in breast cancer