Influence of cellular DNA content on disease-free survival of Stage II breast cancer patients.

Using a novel flow cytometric method to analyze paraffin-embedded archival material, cellular DNA content of the primary tumor was measured in 165 patients with Stage II breast cancer who had been entered onto a large, multicenter trial of adjuvant chemotherapy. Fifty-three (32%) of the tumors examined were diploid, and the remainder contained one or more aneuploid clones. Aneuploid tumors had more extensive axillary lymph node involvement (p less than 0.05 using chi 2 analysis), but there were no significant correlations between cellular DNA content and either menopausal or estrogen receptor status. Forty-nine of 112 (44%) patients with aneuploid tumors have relapsed, compared to 12 of 53 (23%) with diploid tumors, and relapse-free survival curves show that beyond 2 years the diploid group reaches an apparent plateau, with a projected 4-year relapse-free survival of 72%, whereas the aneuploid group shows a continuing risk of relapse with only 43% remaining relapse free at 4 years. This correlation was most pronounced in the premenopausal patients; only 5 of 36 (14%) of those with diploid tumors have relapsed compared to 23 of 63 (37%) in the aneuploid group. However, multivariate analysis using a stepwise Cox model does not thus far confirm an independent prognostic significance of cellular DNA content on disease-free survival compared to node status. The cellular DNA content of the primary tumor did not appear to influence the patients' survival following relapse. These results indicate that compared to aneuploid tumors either diploid tumors have a different natural history or they are more responsive to adjuvant chemotherapy, possibly due to a lower probability of their developing drug resistance.