Premenopausal node-negative breast cancer: May adjuvant chemotherapy be indicated by the analysis of nuclear DNA dynamics?

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Abstract
The management of premenopausal node-negative breast cancer patients is discussed controversially. Accurate cellular as well as biochemical markers are essential for this cancer group to identify high risk patients needing adjuvant chemotherapy. In the present study, flow cytometric DNA analysis (DNA-ploidy status, DNA-index, S-phase fraction, S+(G2+M)-phase fraction) and clinico-pathological variables (clinical stage, tumor size, receptor status, age, histological type and grade) as prognostic factors were determined on paraffin-embedded tumors to predict overall survival (OS) and disease-free survival (DFS). Median observation time was 6.1 years (n = 57). S+(G2+M)-phase fraction was the only flow cytometric DNA predictor of overall survival in the univariate analysis (log-rank test): As compared to the patients with lower S+(G2+M)-phase fraction (≤ 9.3%), patients with S+(G2+M)-phase fraction greater than 9.3% had shorter survival (P = 0.039). Of all the clinico-pathological parameters analyzed (univariate analysis), the survival time was found to be longer when estrogen- and/or progesterone-receptor status was positive (overall survival: P = 0.039; disease-free survival: P = 0.017) and the histological grade was low (overall survival: I + II vs III: P = 0.024; I vs II vs III: P = 0.046). In the multivariate analysis, receptor status was the strongest predictor for overall and disease-free survival. These results suggest that S+(G2+M)-phase fraction in premenopausal node-negative breast cancer could be an additional valuable prognostic factor to classify high risk breast cancer patients needing adjuvant chemotherapy.