Improving the prognostic value of DNA flow cytometry in breast cancer by combining DNA index and S-phase fraction: A proposed classification of DNA histograms in breast cancer

Abstract

To optimize the prognostic value of DNA flow cytometry in breast cancer the authors calculated several parameters from the DNA histogram, including the DNA index, the size and number of aneuploid peaks as well as S‐phase and G2/M‐phase cell cycle fractions. Of these, DNA index and S‐phase fraction (SPF) proved to be the most valuable prognostic indices. DNA aneuploidy was associated with a threefold risk of death as compared to DNA diploidy (P < 0.0001). The highest risk of death was associated with hypertetraploid (>2.20) DNA index, whereas a tetraploid DNA index (1.80–2.20) was associated with a relatively low risk. The SPF had significant additional prognostic value in both DNA diploid (P = 0.0002) and DNA aneuploid (P = 0.02) tumors. By combining DNA index and SPF the authors defined three types of DNA histograms, which were associated with favorable, intermediate, and poor prognosis of the patients. DNA diploidy together with low (2.20) or high (>12%) SPF (type III DNA histogram) was related to the worst prognosis with approximately eight‐fold relative risk of death. In a Cox multivariate regression analysis the type of DNA histogram was an independent and most powerful prognostic indicator in breast cancer. The other independent factors in the Cox analysis were primary tumor size, nodal status, and progesterone receptor status.