title: Primary human breast adenocarcinoma: imaging and histologic correlates of intrinsic susceptibility-weighted MR imaging before and during chemotherapy.
abstract: OBJECTIVE
  To investigate the histopathologic and dynamic magnetic resonance (MR) imaging correlates of intrinsic susceptibility-weighted (ISW) MR imaging in patients with primary human breast adenocarcinoma and to assess the relationship between baseline transverse relaxation rate (R2*) and T2* relaxivity change (ΔR2*) and the response to neoadjuvant chemotherapy (NAC).
  
  
  METHODS
  Institutional ethics approval and informed consent were obtained. Between September 2001 and January 2008, 83 women (median age, 46 years; age range, 26-72 years) with breast cancer were recruited to undergo dynamic contrast medium-enhanced (DCE), dynamic susceptibility contrast-enhanced (DSC), and ISW MR imaging before and after two cycles of NAC. After excluding necrotic, infiltrating, and invasive lobular carcinomas, 31 patients were available for baseline assessment and 27 were available for response assessment. Transfer constant, leakage space, rate constant, initial area under the gadolinium concentration-time curve at 60 seconds, relative blood volume (rBV), relative blood flow (rBF), and R2* were calculated. Relationships between baseline R2* and histopathologic variables (tumor grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor 2 status), tumor size, and dynamic MR imaging parameters were sought. Baseline adenocarcinoma R2* (n = 31) and ΔR2* (n = 27) were correlated with final pathologic response.
  
  
  RESULTS
  Inverse correlations between baseline R2* and rBV (ρ = -0.48, P = .013) and rBF (ρ = -0.44, P = .024) were found, but not after NAC. No relationships were observed between baseline R2* and other kinetic imaging parameters, histopathologic characteristics, or tumor size (P > .05). Baseline R2* values were lower in tumors than in normal breast tissue (31.8 sec(-1) vs 36.2 sec(-1), P = .017) but not after NAC. Increases in R2* were observed after treatment (31.1 sec(-1) vs 34.8 sec(-1), P = .006), with larger increases correlating with pathologic response. ΔR2* was not as effective as DCE or DSC MR imaging parameters in the prediction of response.
  
  
  CONCLUSIONS
  R2* is influenced by blood volume in untreated breast adenocarcinomas. Increases in R2* after two cycles of NAC correlate with pathologic response. Therapy-induced uncoupling of the relationship between R2* and rBV and rBF is consistent with responding tumors becoming hypoxic early during treatment.
  
  
  BACKGROUND
  http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100421/-/DC1.
authors.affiliation: Academic Oncology Unit, Mount Vernon Cancer Centre, Rickmansworth Rd, Northwood, Middlesex HA6 2RN, England. soniali@gmail.com
authors.forename: Sonia P
authors.initials: SP
authors.lastname: Li
authors.forename: N Jane
authors.initials: NJ
authors.lastname: Taylor
authors.forename: Andreas
authors.initials: A
authors.lastname: Makris
authors.forename: Mei-Lin W
authors.initials: ML
authors.lastname: Ah-See
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Beresford
authors.forename: J James
authors.initials: JJ
authors.lastname: Stirling
authors.forename: James A
authors.initials: JA
authors.lastname: d'Arcy
authors.forename: David J
authors.initials: DJ
authors.lastname: Collins
authors.forename: Anwar R
authors.initials: AR
authors.lastname: Padhani
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003287:Contrast Media; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D017404:In Situ Hybridization, Fluorescence; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000473:pathology; D011446:Prospective Studies; D012372:ROC Curve; D018709:Statistics, Nonparametric; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil