title: Staging of locally advanced breast cancer and the prediction of response to neoadjuvant chemotherapy: complementary role of scintimammography and 18F-FDG PET/CT.
abstract: BACKGROUND
  The primary endpoint of the study was to established the role of sestamibi scintimammography and PET/CT findings in locally advanced breast cancer (LABC) before neoadjuvant systemic therapy (NST) in different histological subtypes. The secondary endpoint was to determine the role of FDG PET/CT as multi-drug resistance marker.
  
  
  METHODS
  From January 2012, we prospectively enrolled 51 consecutive women (median age: 49 years; range: 27-76 yrs) with a biopsy-proven LABC. All patients underwent both sestamibi scintimammography and FDG PET/CT within one week before to start NST. Both examinations were qualitatively and semiquantitatively analysed. For scintimammography we calculated the tumor to background ratio (T/B) and the most intense uptake of the tumor to background ratio (I/B) according the following formula: T/B=[cntsT-cntsB]/ [cntsB] and I/B [cntsI-cntsB]/[cntsB]. Furthermore, the percentage washout index (WO) for T and I were obtained, according to: WOT,I= [cntsT,I]early image-[cntsT,I]delayed image/[cntsT,I]early image. Maximum and average (avg) standardized uptake value (SUV) was computed by PET/CT, using a region of interest. Patients who had an evidence of systemic metastases or a second active cancer at imaging scans, were excluded. At the end of pre-operative therapy, the response to therapy was assessed by the analysis of surgical specimen and then correlated with both scintimammographic and PET/CT data.
  
  
  RESULTS
  Based on the inclusion criteria, the final analysis was performed in 49 patients. Scintimammography and PET/CT showed a sensitivity of 100% for the evaluation of primary cancer, while PET/CT showed a slightly higher detection rate for axillary lymph node than scintimammography. According to the biological pattern, SUVmax and SUVavg resulted significantly different among histological subtypes, whereas scintimammographic data did not. At the end of neo-adjuvant therapy, pathological complete response was obtained in 12 (24.4%) patients, while 37 had a partial or no response to NST (identified as no-responders). On the basis of histopathological response to NST, median WOI resulted significantly lower in responders than non-responders (30.5% vs. 44%; P=0.027). Conversely, SUVmax and SUVavg were significantly higher in responders than non-responders (all P<0.05). In this latter subset of patients, high WOTs were associated with low SUVs. On the contrary, in responder group, high SUVs were reported particularly for high WOT values.
  
  
  CONCLUSIONS
  Scintimammography with sestamibi did not accurately determine the responsiveness to therapy. FDG PET/CT is more accurate in the prediction of response to therapy, particularly in the aggressive LABC subtype. Moreover, semiquantitative data by FDG PET seems to be linked with the chemosensitivity to NST.
authors.affiliation: Nuclear Medicine and Molecular Imaging Unit, Veneto Institute of Oncology IOV, IRCCS, Padua, Italy - laura.evangelista@ioveneto.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Evangelista
authors.affiliation: Nuclear Medicine and Molecular Imaging Unit, Veneto Institute of Oncology IOV, IRCCS, Padua, Italy.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Cervino
authors.affiliation: Breast Unit, Veneto Institute of Oncology IOV, IRCCS, Padua, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Michieletto
authors.affiliation: Breast Unit, Veneto Institute of Oncology IOV, IRCCS, Padua, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Saibene
authors.affiliation: Department of Pathology, University Hospital of Padua, Padua, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Orvieto
authors.affiliation: Breast Unit, Veneto Institute of Oncology IOV, IRCCS, Padua, Italy.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bozza
authors.affiliation: Medical Oncology 2 Unit, Oncological Institute of Veneto IOV, IRCCS, Padua, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ghiotto
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008327:Mammography / Q000379:methods; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D020360:Neoadjuvant Therapy / Q000379:methods; D009367:Neoplasm Staging / Q000379:methods; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity; D017256:Technetium Tc 99m Sestamibi; D016896:Treatment Outcome; D051598:Whole Body Imaging / Q000379:methods
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D017256:Technetium Tc 99m Sestamibi