Abstract Background FDG positron emission tomography/computed tomography (PET/CT) may accurately detect distant metastases during staging of primary breast cancer. However, the evidence is very limited. We retrospectively compared the sensitivity and specificity of PET/CT and conventional imaging (CT, ultrasonography, radiography, and skeletal scintigraphy) for the detection of distant metastases in patients with primary breast cancer. We also retrospectively tested the hypothesis that stage III disease detected by conventional imaging + PET/CT has a better prognosis than that detected by conventional imaging only. Methods To determine sensitivity and specificity, we used a database of 225 patients with primary breast cancer (2000-2009) for which PET/CT data existed. The presence or absence of distant metastases was determined based on histopathologic findings, subsequent imaging findings, or clinical follow-up. To determine prognosis, we studied 935 patients newly diagnosed with stage III breast cancer (2000-2009). In 82 of these patients, stage III disease was detected by conventional imaging + PET/CT. We studied 171 IBC patients newly diagnosed with stage III breast cancer. In 51 of these patients, stage III disease was detected by conventional imaging + PET/CT; we compared their relapse-free survival (RFS) and overall survival (OS) rates with those for 853 patients diagnosed using conventional imaging only. Univariate and multivariate Cox Proportional Hazard regression models were used to assess PEC/CT. Results Among 225 pts with primary breast cancer, the sensitivity and specificity for PET/CT in the detection of distant metastases were 97.4% and 91.2%, respectively; This was significantly higher (p=0.009 and P<0.001) than the sensitivity and specificity rates for conventional imaging only (85.9% and 67.3%, respectively). Eleven patients of distant metastases detected by PET/CT were clinically occult and not evident on conventional imaging. Among patients with stage III disease, RFS (hazard ratio [HR]=1.10, p=0.7) and OS (HR=1.14, p=0.673) did not significantly differ based on whether PET/CT was used. RFS also did not show significant difference in multivariate analysis (HR=0.70, p=0.213). However, in inflammatory breast cancer (IBC), patients diagnosed with conventional imaging + PET/CT had longer RFS than patients diagnosed with conventional imaging only in both univariate (HR=0.43, p=0.014) and multivariate analysis (HR=0.33, p=0.004). There was a trend for OS improvement among patients who had PET/CT (HR=0.55, p=0.122). Conclusion PET/CT had higher sensitivity and specificity than conventional imaging in the detection of distant metastases of breast cancer. Among patients with stage III disease, there was no difference in OS or RFS between patients diagnosed with conventional imaging + PET/CT and patients diagnosed with conventional imaging only. IBC patients staged with conventional imaging + PET/CT had better prognosis than those staged with conventional imaging only. Based on our results, the use of PET/CT as a staging tool to detect metastasis is not justified in stage III non-IBC. Conversely, the use of conventional imaging + PET/CT in patients with IBC appears promising, but needs prospective confirmation. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-02.