HIGH DNA CONTENT AND PROGNOSIS IN LYMPH-NODE POSITIVE BREAST-CANCER -A CASE-CONTROL STUDY BY THE UNIVERSITY OF LEIDEN AND ECOG

To investigate whether breast cancer cells with unusually high nuclear DNA content are associated with an adverse outcome, Eastern Cooperati ve Oncology Group investigators selected breast cancer trial patients who suffered an early death (ED) within two years after diagnosis to c ompare with other trial patients who had a survival of at least 7.5 ye ars. Paraffin blocks of primary breast cancers were obtained from 93 e valuable patients who had been enrolled in two surgical adjuvant trial s for lymph node positive (LN +) disease (T1-3N1M0). Single cell monol ayer preparations from these blocks were stained with acriflavine-Feul gen and analyzed by image analysis for DNA content with the automated Leiden Television Analysis System (LEYTAS). Standard prognostic variab les (estrogen receptor(ER) status, number of lymph nodes with metastas es, and size of the cancer) were compared with three DNA content chara cteristics: DNA ploidy status, number of nuclei with > 5 C DNA content , and percent of nuclei with > 5 C. Estimates of the odds ratio in mul tivariate comparisons showed that ER negativity was associated with ED (p = 0.0005) and an odds ratio estimate using negative/positive of 4. 87. The number of positive lymph,nodes associated with ED had a p-valu e of 0.0005 and an odds ratio estimate of 4.63 when comparing the > 3 nodes group to the 1-3 nodes group. In contrast, the strongest associa tion for any of the DNA content characteristics with ED had a p-value of 0.017 and an odds ratio estimate of 2.76. This power of association disappeared when stratified on ER status. Therefore, the presence of breast cancer cells with highly aneuploid (i.e. > 5 C) DNA content doe s not possess independent prognostic information in LN + breast cancer . An association remains to be tested in lymph node negative breast ca ncer.