title: DNA ploidy is an independent predictor of survival in breast invasive ductal carcinoma: a long-term multivariate analysis of 393 patients.
abstract: OBJECTIVE
  To evaluate "classic" prognostic parameters, as well as DNA ploidy and S-phase fraction (SPF), in relation to disease-free (DFS) and disease-specific (DSS) survival in breast invasive ductal carcinoma (IDC) with long-term follow-up study.
  
  
  METHODS
  The study involved 393 patients with IDC and median follow-up of 134 months (50-240). Histological grading, tumor size, axillary nodal involvement, pathological staging and hormone receptor status were considered as established prognostic markers. Ploidy and SPF 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 105 (26.7 %) deaths and 140 (35.6 %) disease recurrences during follow-up. Two hundred thirty-one (58.8 %) tumors were aneuploid. High SPF and aneuploidy were associated with tumors with higher grade of differentiation, greater size and negative hormone receptors. Higher SPF and advanced disease stage are correlated. In univariate analysis, all the clinicopathological and cytometric features, including patients <40 years and a subgroup presenting hypertetraploid/multiploid tumors, are significantly correlated with clinical outcome, apart from SPF and estrogen receptors for DFS. In multivariate analysis, nodal involvement, DNA aneuploidy and lack of progesterone receptors (for DSS) retained statistically significant association with shorter survival. In node-negative patients, ploidy (for DFS) and estrogen receptors (for DSS) significantly predicted survival. In both subgroups of node-positive patients and those (n = 195) with intermediate differentiation tumors (G2), aneuploidy was an indicator of worse prognosis.
  
  
  CONCLUSIONS
  Along with nodal status and hormone receptor expression, DNA ploidy is an independent predictor of long-term survival in IDC.
authors.affiliation: Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa, EPE, Lisbon, Portugal. aepinto@ipolisboa.min-saude.pt
authors.forename: António E
authors.initials: AE
authors.lastname: Pinto
authors.forename: Teresa
authors.initials: T
authors.lastname: Pereira
authors.forename: Márcia
authors.initials: M
authors.lastname: Santos
authors.forename: Mariana
authors.initials: M
authors.lastname: Branco
authors.forename: Angelo
authors.initials: A
authors.lastname: Dias
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; D000782:Aneuploidy; D001943:Breast Neoplasms / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016196:S Phase; D013997:Time Factors; D055815:Young Adult
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone