title: [DNA ploidy is an independent prognostic biomarker in breast invasive ductal carcinoma].
abstract: OBJECTIVE
  To evaluate 'classic' prognostic parameters, as well as DNA ploidy and S-phase fraction, in relation to disease-free and overall survival in breast invasive ductal carcinoma with long-term follow-up.
  
  
  METHODS
  The study involved 400 patients with breast invasive ductal carcinoma and median follow-up of 134 months (50-240). Histological grading, tumour size, axillary nodal involvement, pathological staging and hormone-receptor status were assessed as established prognostic markers. Ploidy and S-phase fraction were determined prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables.
  
  
  RESULTS
  There were 106 deaths (26.5%) and 141 disease recurrences (35.2%) during follow-up. Two hundred thirty-five (58.7%) tumours were aneuploid. High S-phase fraction and aneuploidy were associated with tumours with higher grade of differentiation, greater size and negative hormonal receptors. In univariate analysis, all the clinicopathological and cytometric features (including patients < 40 years and a subgroup presenting hipertetraploid/multiploid tumours), but S-phase fraction and estrogen receptors for disease free survival, significantly correlated with clinical outcome. In multivariate analysis, advanced disease stage, DNA aneuploidy and lack of progesterone receptors retained statistically significant association with shorter survival. In the subgroup of patients with intermediate differentiation tumours (G2), aneuploidy associated with worse prognosis. In the subset of node-negative patients, only estrogen receptors showed significant correlation with disease evolution. In node-positive patients, greater size tumours and aneuploidy (in relation to overall survival) were indicators of worse prognosis.
  
  
  CONCLUSIONS
  Along with disease staging and hormone-receptor expression, DNA ploidy is an independent prognostic biomarker of long-term survival in breast invasive ductal carcinoma.
authors.affiliation: Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Lisboa, Portugal.
authors.forename: António E
authors.initials: AE
authors.lastname: Pinto
authors.forename: Teresa
authors.initials: T
authors.lastname: Pereira
authors.forename: Giovani L
authors.initials: GL
authors.lastname: Silva
authors.forename: Mónica C
authors.initials: MC
authors.lastname: Ferreira
authors.forename: Saudade
authors.initials: S
authors.lastname: André
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000401:mortality; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008875:Middle Aged; D011003:Ploidies; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D005819:Genetic Markers