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Background We evaluated the relationship between 18F-FDG uptake and mitochondrial activity in cancer cells and investigated the prognostic implications thereof in patients with invasive ductal carcinoma of the breast (IDCB). Methods In total, 150 consecutive patients with IDCB who underwent preoperative 18F-FDG PET/CT followed by curative surgical resection were retrospectively enrolled. Mitochondrial activity of cancer cells was assessed based on translocase of outer mitochondrial membrane 20 (TOMM20) expression and cytochrome C oxidase (COX) activity. Pearson's correlation analysis was used to assess the relationship between SUVmax of the primary tumour (pSUVmax) and mitochondrial activity. Clinicopathological factors, including pSUVmax, histological grade, expression of ER, PR, HER2, and TOMM20, and COX activity, were assessed for prediction of progression-free survival (PFS). The Kaplan–Meier method and Cox proportional hazards model were used for the survival analysis. Results Sixteen of the 150 subjects (10.7%) showed progression during the follow-up period. pSUVmax correlated significantly and positively with TOMM20 expression and COX activity. Univariate analysis revealed that pSUVmax, TOMM20 expression, COX activity, ER and PR status, and histologic grade were significantly associated with PFS. Multivariate analysis revealed a significant difference in pSUVmax (HR, 4.50; 95% CI, 1.43–14.17; P = 0.010). Conclusions There was a significant positive correlation between 18F-FDG uptake and mitochondrial activity of cancer cells in patients with IDCB. Increased 18F-FDG uptake and mitochondrial activity were significantly associated with a shorter PFS. Therefore, assessment of preoperative 18F-FDG uptake and post-surgical mitochondrial activity in patients with IDCB could be used as marker for prediction of PFS. Legal entity responsible for the study Choi Byung Wook (Daegu Catholic University Medical Center). Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]