title: Correlation of hypoxia inducible transcription factor in breast cancer and SUVmax of F-18 FDG PET/CT.
abstract: BACKGROUND
  Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed.
  
  
  METHODS
  Two-hundred seven female patients with IDC who underwent pretreatment fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) were enrolled. The pSUVmax was compared with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), axillary lymph node (LN) metastasis, stage and HIF-1a expression. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method.
  
  
  RESULTS
  pSUVmax was significantly higher in patients with HIF-1a expression ≥ 2 compared to patients with HIF-1a expression < 2 (5.2 ± 4.5 vs. 3.7 ± 3.1, p = 0.008). pSUVmax was also significantly higher in higher stage (p < 0.000001), ER-negative tumors (p < 0.0001), PR-negative tumors (p = 0.0011) and positive LN metastasis (p = 0.0013). pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (6.8 ± 4.4 vs. 4.1 ± 3.7, p = 0.0005). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.51 to be the optimal cutoff for predicting PFS (sensitivity: 53.6%, specificity: 86.0%). Patients with high pSUVmax (> 6.5) had significantly shorter PFS compared to patients with low pSUVmax (p < 0.0001).
  
  
  CONCLUSIONS
  pSUVmax on pretreatment F-18 FDG PET/ CT reflect expression of HIF-1a and can be used as a good surrogate marker for the prediction of progression in patients with IDC. The amount of FDG uptake is determined by the presence of glucose metabolism and hypoxia in breast cancer cell.
authors.forename: Young-Ju
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Jung
authors.forename: Yoon-Young
authors.initials: YY
authors.lastname: Cho
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Hoon-Kyu
authors.initials: HK
authors.lastname: Oh
authors.affiliation: Department of Nuclear Medicine, Catholic University of Daegu School of Medicine. kufa77@hanmail.net.
authors.forename: Sungmin
authors.initials: S
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods / Q000706:statistics & numerical data; D015995:Prevalence; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate; D000072258:Tumor Hypoxia
chemical_list: D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: F-18 FDG PET/CT; HIF-1α; Invasive ductal cancer of breast; SUVmax