Positron emission tomographic assessment of 'metabolic flare' to predict response of metastatic breast cancer to antiestrogen therapy

We have investigated whether increased tumor uptake of fluorine-18 fluorodeoxyglucose (FDG) detected with positron emission tomography (PET) early after initiating tamoxifen therapy ('metabolic flare') predicts a hormonally responsive breast cancer. Eleven postmenopausal women with biopsy-proved estrogen receptor-positive (ER+) metastatic breast cancer were studied by PET with FDG and 16α[¹⁸F]fluoro-17β-estradiol (FES) before and 7-10 days after initiation of tamoxifen therapy. FDG and FES uptake was evaluated semiquantitatively in 21 lesions. The PET results were correlated with follow-up evaluation. continued until the patient be came unresponsive to hormone therapy (3-24 months). There were seven responders and four nonresponders based on clinical follow-up. None of the responders had a clinical flare reaction, but all demonstrated metabolic flare, with a mean ± standard deviation increase in tumor standardized uptake value (SUV for FDG of 1.4 ± 0.7. No evidence for flare was noted in the nonresponders (change in SUV for FDG -0.1 ± 0.4; P = 0.008 vs. responders). The degree of ER blockade by tamoxifen was greater in responders (mean decrease in SUV 2.7 ± 1.7) than in nonresponders (mean decrease 0.8 ± 0.5) (P = 0.04). The lesions of responders had higher baseline SUVs for FES than did those of three of four nonresponders (≥ 2.2 vs ≤ 1.7). The findings of a metabolic flare by FDG-PET and the degree of ER blockade by FES-PET early after institution of tamoxifen treatment appear to predict responsiveness to antiestrogen therapy in patients with ER+ metastatic breast cancer.