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 16 alpha[F-18]fluoro-17 beta-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; re-spenders). 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 base line SUVs for FES than did those of three of four nonresponders (greater than or equal to 2.2 vs less than or equal to 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.