Prognostic significance of DNA measurements in 409 consecutive breast cancer patients

Abstract

Four hundred nine consecutive breast cancer patients were studied retrospectively. Microspectrophotometric DNA measurements were performed using archival, fine-needle slide preparations upon which the primary diagnoses had been based 8 to 13 years earlier. The DNA distribution patterns of the tumor cell populations were analyzed according to various criteria and the cytochemical data were correlated to the clinical course, defined as distant recurrence-free survival. The results demonstrated a strong relationship between nuclear DNA content of the breast cancer cells and prognosis. Tumors exhibiting DNA values within the limits of normal tissues (DNA euploidy) were found to be correlated with a favorable prognosis. In contrast, tumors with increased and scattered DNA values (DNA aneuploidy) were found indicative of poor prognosis. This was found to be the case regardless whether the percentage of cells above 2.5c or 5c, DNA index/modal value, or the histogram typing according to Auer et al were utilized to discriminate low-grade from high-grade malignant cases. All of these DNA variables were also shown to be significantly correlated. With the aid of the Cox regression method, the additional prognostic value of any given variable was tested against the others. The statistical analyses showed that the histogram typing gives significant prognostic information in addition to that provided by any other variable. In conclusion, the current study demonstrates that tumor nuclear DNA content is a strong indicator of prognosis in patients suffering from invasive breast adenocarcinoma. However, the results also show that simple determination of the stemline position is not the optimal DNA measure of intrinsic tumor malignancy potential. The fraction of cells scattered outside the modal peaks of the histograms are of utmost importance for adequate cytochemical malignancy grading in breast carcinomas.