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Aim To evaluate the feasibility of early metabolic response assessment with 18F-FDG PET/CT in patients with breast cancer liver metastases 4 weeks after radioembolization with Yttrium-90 labeled microspheres. Methods 25 patients (mean age 58y, range 40–74) with advanced stage liver metastases of breast cancer were treated with 1.9 ± 0.4 GBq of 90Y-microspheres in the salvage setting and underwent 18F-FDG PET/CT at baseline and 4 weeks post-radioembolization. 14 patients (56 %) had an excessive hepatic tumor burden (> 50 % of total liver volume), 21 patients (84 %) had extrahepatic disease. Liver lesions with the highest SUVmax were selected as target lesions and a cut-off was set at 50 % reduction to separate responders from non-responders. The predictive impact of metabolic response on overall survival (OS) was investigated along with other prognostic factors. Results The median OS in this highly advanced metastatic cohort was 7 months (95 % CI, 5–9). All patients had a reduction in SUVmax (mean ΔSUVmax: –49 ± 26 %) at 4 weeks post-treatment. Patients with > 50 % SUVmax reduction survived longer (median OS 13 mo, 95 % CI 8–18) than the remaining patients (median OS 4 mo, 95 % CI 2–6; p = 0.001). From all investigated baseline factors including age, performance status, and presence of extra-hepatic disease, only the hepatic tumor burden had a significant impact on OS (p = 0.02). Conclusions This is the first preliminary evidence in breast cancer that early post-radioembolization molecular response assessment of treated liver metastases – as early as 4 weeks posttreatment – may predict survival. If confirmed by larger series, FDG PET/CT could be considered for early response-adapted treatment modifications.