DNA ploidy and percent S-phase as prognostic factors in node-positive breast cancer: results from patients enrolled in two prospective randomized trials.

Abstract

PURPOSE AND METHODS To help clarify the clinical utility of flow-cytometric parameters, we performed flow cytometry on archival paraffin-embedded primary breast cancers from 502 patients treated on two adjuvant chemotherapy protocols performed by the North Central Cancer Treatment Group (NCCTG) and Mayo Clinic. DNA ploidy and percent S-phase (%S) were examined in univariate and Cox model multivariate analyses along with tumor size, menopausal and estrogen receptor status, Quetelet's index (QI), number of positive nodes and nodes examined, and Fisher and nuclear grades. RESULTS Ploidy analysis showed that 40% of tumors were DNA diploid and 60% were DNA nondiploid (12% tetraploid and 48% aneuploid). There was no difference in relapse-free survival (RFS) (P = .82) or overall survival (OS) (P = .78) between the ploidy groups. Tetraploid patients had the longest RFS and OS of any group, but this did not achieve statistical significance. The %S was computed in 98% of cases and the medians were 9.0% for all patients, 6.4% for diploid patients, and 11.7% for nondiploid patients (P < .0001). By use of a %S greater than 12.3 as a prognostic variable in a univariate analysis, there was a significant difference in the RFS (P = .02) and OS (P = .007) of patients with low- versus high-proliferative tumors. However, when the %S was adjusted for clinical characteristics in the multivariate analysis, it was not a significant factor for RFS (P = .23) or OS (P = .36). CONCLUSION These results indicate that DNA content and %S measurements by flow cytometry are not clinically useful independent prognostic factors in women with resected node-positive breast cancer administered adjuvant chemotherapy.