title: p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen according to breast cancer molecular classes.
abstract: BACKGROUND
  We hypothesized that, among molecular subclasses of breast cancer, p53 status may have a differential predictive value for the efficacy of anthracyclines/alkylating agents-based regimen. We analysed the efficacy of a preoperative combination between 5-fluorouracil, anthracyclines and cyclophosphamide according to both p53 status and molecular classification.
  
  
  METHODS
  Oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) expression and p53 status were determined by immunohistochemistry in 293 samples from two different centres. A logistic regression model was used for multivariate analysis of predictors for pathological complete response (pCR).
  
  
  RESULTS
  p53 immunostaining (54%) was associated with high grade (P = 0.002) and ER negativity (P = 0.04). p53 was detected in 59% of triple-negative tumours (ER-/PgR-/HER2-, n = 120 patients). In the overall population, pCR (9.6%) was independently predicted by high tumour grade (P = 0.002) and ER/PgR/HER2 triple negativity (P = 0.0004), but not by p53 status (P = 0.12). p53 immunostaining was associated with a trend for a higher rate of pCR in triple-negative tumours [relative risk (RR) = 2.5, 95% confidence interval (CI) = 0.8-7.5, P = 0.09], but not in non-triple-negative tumours (RR = 0.73, 95% CI = 0.16-3.3, P = 0.69).
  
  
  CONCLUSIONS
  p53 status may have a different predictive value for efficacy of anthracycline/alkylating agents-based regimen in each molecular subclass, a result which may explain the different results reported in literature.
authors.affiliation: Department of Pathology, Institut Gustave Roussy, Villejuif.
authors.forename: F-C
authors.initials: FC
authors.lastname: Bidard
authors.affiliation: Department of Pathology, Institut Gustave Roussy, Villejuif.
authors.forename: M-C
authors.initials: MC
authors.lastname: Matthieu
authors.affiliation: Department of Medical Oncology.
authors.forename: P
authors.initials: P
authors.lastname: Chollet
authors.affiliation: Department of Pathology, Centre Jean Perrin, Clermont-Ferrand.
authors.forename: I
authors.initials: I
authors.lastname: Raoefils
authors.affiliation: Department of Medical Oncology.
authors.forename: C
authors.initials: C
authors.lastname: Abrial
authors.affiliation: Department of Medical Oncology and Translational Research Unit, UPRES03535, Université Paris Sud, Institut Gustave Roussy, Villejuif, France.
authors.forename: J
authors.initials: J
authors.lastname: Dômont
authors.affiliation: Department of Medical Oncology and Translational Research Unit, UPRES03535, Université Paris Sud, Institut Gustave Roussy, Villejuif, France.
authors.forename: M
authors.initials: M
authors.lastname: Spielmann
authors.affiliation: Department of Medical Oncology and Translational Research Unit, UPRES03535, Université Paris Sud, Institut Gustave Roussy, Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Delaloge
authors.affiliation: Department of Medical Oncology and Translational Research Unit, UPRES03535, Université Paris Sud, Institut Gustave Roussy, Villejuif, France. Electronic address: fandre@igr.fr.
authors.forename: F
authors.initials: F
authors.lastname: André
authors.affiliation: Department of Pathology, Centre Jean Perrin, Clermont-Ferrand.
authors.forename: F
authors.initials: F
authors.lastname: Penault-Llorca
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000145:classification* / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D016896:Treatment Outcome; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D018943:Anthracyclines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53