DNA histogram analysis for node-negative breast cancer.

Abstract

The combination of DNA ploidy and S-phase is one of the strongest general prognostic indicators for node-negative breast cancer (1). The costs associated with this prognostic power are relatively minimal; laboratory total processing time is usually less than 10 min and reagents are relatively inexpensive. The test can be standardized world-wide as long as strict guidelines are followed, and the test’s result can be presented in a way that is easily understood by oncologists. DNA ploidy and S-phase prognostic strength can be further augmented by other wellknown prognostic indicators, such as menopausal status and primary tumor size. Figures 1 and 2 provide evidence for the above statements (1). Figure 1A shows highly significant relapse-free survival (RFS) stratifications for over 935 node-negative patients in the Baylor study. The stratifications are based on a prognostic model composed of an optimal combination of adjusted DNA ploidy and S-phase. When the same prognostic model and stratification boundaries are applied to other independent studies (see Fig. 1B and C), similar highly-significant patient stratifications are observed. Figure 2 demonstrates how the prognostic model can be further augmented by primary size and menopausal status. These patient stratifications are potentially important for managing this prevalent and deadly disease. In 1999, the incidence of breast cancer in the United States was over 170,000; greater than leukemia, lymphoma, and AIDS combined. In 2003, it is predicted to be over 200,000. Most of these cases are discovered before the tumor has infiltrated into the patient’s nodes (node-negative); therefore, this diagnostic test can potentially impact the strategy for optimal treatment for this large patient group. The DNA histogram test can be divided into four processing steps: sample preparation, DNA histogram acquisition, cell-cycle analysis, and final processing. In order for cytometrists to perform this test to its full capability, the following guidelines for each of these steps are recommended.