Correlation of cell-cycle kinetics, hormone receptors, histopathology, and nodal status in human breast cancer

DNA ploidy and percent of (%S-phase) S-phase cells were determined from the DNA content distribution of 21 benign and 76 malignant (69 primary, 7 metastatic) breast tumors using flow cytometry. All of the benign tumors were diploid, whereas 89% of the malignant tumors had measurable aneuploidy. Multiple stem-lines were observed in approximately 10% of the malignant tumors. The ploidy distribution of the malignant tumors was bimodal with an increased frequency of tumors with a near diploid DNA index (DI), and a second group with DI ranging from triploid to tetraploid. The percentage of cells in S-phase ranged from less than 1% to 37.4%. DI and %S were significantly higher in poorly differentiated duct carcinomas, medullary carcinomas, and recurrent tumor metastases. DI and %S were also significantly higher in estrogen-receptor-negative tumors. There was no correlation between DI or %S and the extent of axillary nodal metastases. However, within the groups of node-negative and node-positive patients, DI and %S were not randomly distributed but were significantly correlated with degree of nuclear differentiation. Both parameters were higher in poorly differentiated tumors compared with well-differentiated tumors, indicating significant intrastage heterogeneity in tumor ploidy and proliferation characteristics. Determination of the prognostic significance of DI and %S will require a longer follow-up time.