Association of DNA index and S-phase fraction with prognosis of nodes positive early breast cancer.

DNA index and S-phase fraction of 490 primary breast carcinomas were measured by flow cytometry, using paraffin-embedded tissue as a starting point. All patients had involvement of axillary lymph nodes and all were randomized onto one of the Ludwig Breast Cancer Trials I-IV between July 1978 and August 1981. The presence of an abnormal DNA stemline correlated with involvement of four or more axillary lymph nodes (P = 0.09), postmenopausal status (P = 0.008), estrogen receptor negativity (P = 0.03), and high tumor grade (P = 0.0005). Disease-free and overall survival for these patients was worse than for those with tumors of normal DNA content, but DNA aneuploidy did not have independent prognostic significance when allowance was made for its correlation with other prognostic features. The percentage of cells in S phase, which is an index of cell proliferation, was also analyzed in 285 DNA histograms considered to be capable of giving a valid estimate. Disease-free survival for 154 patients with S phase less than or equal to 10% was significantly longer than for those with S phase greater than 10% (P = 0.0008). S-phase greater than 10% was strongly correlated with high tumor grade (P less than 0.00001) and abnormal DNA index (P less than 0.00001) but only weakly correlated with nodal, hormone receptor, and menopausal status. Multivariate analysis using a Cox proportional hazard model suggested that the prognostic significance of the percentage of S phase was related to the association with tumor grade. Because it gives rapid, objectively determined information about biological aggressiveness DNA flow cytometry may well establish a role in routine clinical practice, but further technical refinements are required before it can be used for treatment decision making in nodes positive early breast cancer patients.