PROGNOSTIC-SIGNIFICANCE OF TUMOR DNA CONTENT AND S-PHASE FRACTION BY FLOW-CYTOMETRY IN NODE-POSITIVE BREAST CARCINOMAS

Purpose - This study was aimed at evaluating the prognostic value of t umor DNA content in patients with node-positive breast carcinoma submi tted or not to adjuvant therapy. Patients and Methods - Tumor DNA cont ent and S phase fraction (SPF) were evaluated by flow-cytometry on for malin-fixed paraffin embedded material from 761 tumors resected betwee n 1980 and 1986. Of these patients, 199 (26.1%) received no adjuvant t herapy while the others were submitted to adjuvant chemotherapy or hor mone therapy. The follow up ranged from 2.5 to 9.5 years (average: 6.5 years). Results - Of the 761 cases, 320 (42%) were diploid and 441 (5 8%) were aneuploid. Diploidy with low SPF was a good marker of better prognosis when compared to aneuploidy or diploidy with high SPF (p = 0 .0044). The prognostic advantage of diploidy with low SPF over aneuplo idy or diploidy with high SPF was however only significant in the subg roup of patients not submitted to adjuvant chemotherapy or hormone the rapy (p = 0.0012) and was independent of other prognostic factors. Ane uploidy was associated with an older age at diagnosis (p = 0.009), poo r nuclear grade (p <0.0001), absence of progesterone receptors (p = 0. 012), Her2/neu oncoprotein expression (p = 0.001) heat-shock protein-2 7 staining (p = 0.042) and cathepsin D expression (p = 0.005). Diploid y with high SPF was associated with larger tumor size (p = 0.001) and more weakly with high nuclear grade (p = 0.066) and a younger age (p = 0.069). Conclusions - This study re-emphasizes the association of dip loidy and low SPF with a better prognosis in node-positive breast carc inoma. It also suggests that the prognostic significance of DNA ploidy may be influenced by the addition of adjuvant therapy.