Intracellular hypoxia measured by 18F-fluoromisonidazole positron emission tomography has prognostic impact in patients with estrogen receptor-positive breast cancer

Background Hypoxia is a key driver of cancer progression. We evaluated the prognostic impact of .sup.18F-fluoromisonidazole (FMISO) prior to treatment in patients with breast cancer. Methods Forty-four patients with stage II/III primary breast cancer underwent positron emission tomography/computed with .sup.18F-fluorodeoxyglucose (FDG-PET/CT) and FMISO. After measurement by FDG-PET/CT, the tissue-to-blood ratio (TBR) was obtained using FMISO-PET/CT. FMISO-TBR was compared for correlation with clinicopathological factors, disease-free survival (DFS), and overall survival (OS). Multiplex cytokines were analyzed for the correlation of FMISO-TBR. Results Tumors with higher nuclear grade and negativities of estrogen receptor (ER) and progesterone receptor had significantly higher FMISO-TBR than other tumors. Kaplan-Meier survival curves showed that patients with a higher FMISO-TBR (cutoff, 1.48) had a poorer prognosis of DFS (p = 0.0007) and OS (p = 0.04) than those with a lower FMISO-TBR. Multivariate analysis indicated that higher FMISO-TBR and ER negativity were independent predictors of shorter DFS (p = 0.01 and 0.03). Higher FMISO-TBR was associated with higher plasma levels of angiogenic hypoxic markers such as vascular endothelial growth factor, transforming growth factor-[alpha], and interleukin 8. Conclusions FMISO-PET/CT is useful for assessing the prognosis of patients with breast cancer, but it should be stratified by ER status. Trial registration UMIN Clinical Trials Registry, UMIN000006802. Registered on 1 December 2011. Keywords: Breast cancer, Hypoxia, Prognosis, .sup.18F-fluoromisonidazole, Positron emission tomography