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

Abstract. 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 became 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.