title: Evaluation of HER2 and p53 expression in predicting response to docetaxel-based first-line chemotherapy in advanced breast cancer.
abstract: BACKGROUND
  The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer.
  
  
  METHODS
  HER2 and p53 expression was analysed in 36 (median age 55 yrs; range 37-87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy. HER2 was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), p53 was tested by IHC. We correlate the expression of study parameters with pathologic parameters, RECIST response and survival. The standard cut-off value of 2 was used to determine HER2 overexpression while p53 mean expression level was used to divide low/high expressors tumors.
  
  
  RESULTS
  Median time to progression and overall survival were 9 (range 2-54) and 20 (range 3-101) months. Overall response rate was 41.6%. Nine cases showed HER2 overexpression. HER2 was more frequently overexpressed in less differentiated (p=0.05) and higher stage (p=0.003) disease. Mean FISH-HER2 values were significantly higher in responder than in non-responder pts (8.53±10.21 vs 2.50±4.12, p=0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (p=0.046). p53 expression was only associated with higher stage disease (p=0.02) but lack of any significant association with HER status or docetaxel response. No significant relation with survival was observed for any parameter.
  
  
  CONCLUSIONS
  Our data seem to indicate that FISH-determined HER2 status but not p53 is associated with docetaxel sensitivity in metastatic breast cancer.
authors.affiliation: Oncology Department, Medical Oncology Division, AUSL12 di Viareggio and Istituto Toscano Tumori-Versilia Hospital, Lido di Camaiore, Italy. andreacamerini@katamail.com
authors.forename: Andrea
authors.initials: A
authors.lastname: Camerini
authors.forename: Sara
authors.initials: S
authors.lastname: Donati
authors.forename: Paolo
authors.initials: P
authors.lastname: Viacava
authors.forename: Olimpia
authors.initials: O
authors.lastname: Siclari
authors.forename: Cheti
authors.initials: C
authors.lastname: Puccetti
authors.forename: Gianna
authors.initials: G
authors.lastname: Tartarelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Valsuani
authors.forename: Filomena
authors.initials: F
authors.lastname: De Luca
authors.forename: Leonardo
authors.initials: L
authors.lastname: Martini
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavazzana
authors.forename: Domenico
authors.initials: D
authors.lastname: Amoroso
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000601:surgery; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D000970:Antineoplastic Agents; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C508053:ERBB2 protein, human