title: MR mammography using diffusion-weighted imaging in evaluating breast cancer: a correlation with proliferation index.
abstract: OBJECTIVE
  To evaluate whether the variation of the apparent diffusion coefficient (ADC) values obtained with DWI can predict elevated levels of Ki67 proliferation index and aggressive subtypes in patients with breast cancer.
  
  
  METHODS
  Breast MRI studies of 115 patients (mean age 57.3 years, range 36-81 years) with a biopsy-proven breast cancers were evaluated in this retrospective IRB-approved study. Examinations were performed on a 1.5 T magnet and included a Single-Shot Echoplanar DWI sequence with b values of 0 and 1000 s/mm(2). For each target lesion, ADC was measured. ADC values were compared considering Ki67 status (≥20 % or <20 %), histology, grade (G1, G2 or G3) and clinical-pathological classification (Luminal A, Luminal B HER2-positive, Luminal B HER-2 negative, HER-2 enriched and Triple Negative). Mann-Whitney U test and Kruskal-Wallis test were used for comparisons and receiver operating characteristic (ROC) curves were obtained. Inter- and intra-reader variability was evaluated in a subset of 40 patients, using interclass correlation coefficient (ICC) and Bland-Altman plots.
  
  
  RESULTS
  Of 115 lesions, 53 (46.1 %) were assessed as Ki67 positive and 62 (53.9 %) as Ki67 negative. ADC values were significantly (p < 0.0001) lower in Ki67-positive patients (median 0.86 × 10(-3) mm(2)/s; interquartile range 0.75-0.92) compared to Ki67-negative (median 1.03 × 10(-3) mm(2)/s; interquartile range 0.92-1.13). Median ADC was also lower in G2 and G3 cancer and in the Luminal B Her2-negative subtype (p = 0.0015). No differences were found when evaluating histology. ROC curve showed a sensitivity and specificity of 83.0 and 66.1 %, respectively, when using a cutoff of 0.95 s/mm(2) to differentiate Ki67-positive from Ki67-negative cancers. Inter- and intra-reader variability was moderate (ICC = 0.623; ICC = 0.548, respectively). No systematic differences were identified with Bland-Altman plots.
  
  
  CONCLUSIONS
  Lower ADC values are associated with elevated Ki67 proliferation index and more aggressive pathologic features. Moderate agreement in ADC measurement could be a limitation.
authors.affiliation: Department of Medical and Biological Sciences, Institute of Diagnostic Radiology, Azienda Ospedaliero-Universitaria, "S.Maria della Misericordia", P.le Santa Maria della Misericordia, University of Udine, Udine, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Molinari
authors.affiliation: Department of Medical and Biological Sciences, Institute of Diagnostic Radiology, Azienda Ospedaliero-Universitaria, "S.Maria della Misericordia", P.le Santa Maria della Misericordia, University of Udine, Udine, Italy. clauser.p@hotmail.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Clauser
authors.affiliation: Department of Medical and Biological Sciences, Institute of Diagnostic Radiology, Azienda Ospedaliero-Universitaria, "S.Maria della Misericordia", P.le Santa Maria della Misericordia, University of Udine, Udine, Italy.
authors.forename: Rossano
authors.initials: R
authors.lastname: Girometti
authors.affiliation: Department of Medical and Biological Sciences, Institute of Diagnostic Radiology, Azienda Ospedaliero-Universitaria, "S.Maria della Misericordia", P.le Santa Maria della Misericordia, University of Udine, Udine, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Linda
authors.affiliation: Department of Medical and Biological Sciences, Institute of Diagnostic Radiology, Azienda Ospedaliero-Universitaria, "S.Maria della Misericordia", P.le Santa Maria della Misericordia, University of Udine, Udine, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cimino
authors.affiliation: Department of Oncology, Azienda Ospedaliero-Universitaria, "S.Maria della Misericordia", University of Udine, Udine, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Puglisi
authors.affiliation: Department of Medical and Biological Sciences, Institute of Diagnostic Radiology, Azienda Ospedaliero-Universitaria, "S.Maria della Misericordia", P.le Santa Maria della Misericordia, University of Udine, Udine, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Zuiani
authors.affiliation: Department of Medical and Biological Sciences, Institute of Diagnostic Radiology, Azienda Ospedaliero-Universitaria, "S.Maria della Misericordia", P.le Santa Maria della Misericordia, University of Udine, Udine, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bazzocchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008327:Mammography / Q000379:methods*; D008875:Middle Aged; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases; D012189:Retrospective Studies
chemical_list: D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast neoplasms; Diffusion-weighted imaging; Ki67 antygen; Magnetic resonance imaging; Tumor markers