title: Correlation of breast cancer subtypes, based on estrogen receptor, progesterone receptor, and HER2, with functional imaging parameters from ⁶⁸Ga-RGD PET/CT and ¹⁸F-FDG PET/CT.
abstract: OBJECTIVE
  Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes.
  
  
  METHODS
  In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6 ± 7.5 years old). (68)Ga-Labeled arginine-glycine-aspartic acid (RGD) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUVmax and SUVavg) from RGD PET/CT and SUVmax and SUVavg from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2-, ER/PR+,Her2+, ER/PR-,Her2+, and ER/PR-,Her2-), were considered.
  
  
  RESULTS
  Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88 ± 8.73 vs 10.48 ± 6.01, p = 0.02 for SUVmax; 9.40 ± 5.19 vs 5.92 ± 4.09, p = 0.02 for SUVavg) and the PR-negative group (8.37 ± 4.94 vs 4.79 ± 3.93, p = 0.03 for SUVavg). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42 ± 0.59 vs 2.90 ± 0.75, p = 0.04 for SUVmax; 1.60 ± 0.38 vs 1.95 ± 0.53, p = 0.04 for SUVavg) and showed a significant positive correlation with the HER2/CEP17 ratio (r = 0.38, p = 0.03 for SUVmax and r = 0.46, p < 0.01 for SUVavg). FDG PET parameters showed significantly higher values in the ER/PR-,Her2- subgroup versus the ER/PR+,Her2- or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER/PR-,Her2- subgroup versus the other subgroups. There was no correlation between FDG and RGD PET parameters in the overall group. Only the ER/PR-,Her2- subgroup showed a significant positive correlation between FDG and RGD PET parameters (r = 0.59, p = 0.03 for SUVmax).
  
  
  CONCLUSIONS
  (68)Ga-RGD and (18)F-FDG PET/CT are promising functional imaging modalities for predicting biomarkers and molecular phenotypes in breast cancer patients.
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: Hai-Jeon
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Keon Wook
authors.initials: KW
authors.lastname: Kang
authors.forename: In Kook
authors.initials: IK
authors.lastname: Chun
authors.forename: Nariya
authors.initials: N
authors.lastname: Cho
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Jeong
authors.forename: Song
authors.initials: S
authors.lastname: Lee
authors.forename: Kyeong Cheon
authors.initials: KC
authors.lastname: Jung
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Moon
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D056831:Coordination Complexes; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008875:Middle Aged; D064847:Multimodal Imaging; D009842:Oligopeptides; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor; D056831:Coordination Complexes; D019788:Fluorodeoxyglucose F18; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C584295:68Ga-1,4,7-triazacyclononane-1,4-7-triacetic acid-isothiocyanatobenzyl-c(Arg-Gly-Asp-Tyr-Lys); C508053:ERBB2 protein, human