S-phase fraction identifies high-risk subgroups among DNA-diploid breast cancers

The prognostic value of DNA content measured by means of flow cytometry was analyzed in formalin-fixed, paraffin-embedded samples from 231 breast cancer patients treated between 1984 and 1988, with a mean follow-up period of 55 months. We followed the guidelines of a Consensus Meeting held on this issue in Maine, USA, in 1992. DNA-diploid and -aneuploid tumors were evaluated separately for the fraction of cells in S-phase (SPF) contained in them, this being divided into three groups ('high', 'intermediate', and 'low'), defined by the 25th and 75th centile of the SPF-distribution corresponding to either DNA-diploid or DNA-aneuploid tumors. Unequivocally readable histograms were obtained from 174 samples (75.3%). A high SPF in diploid tumors was significantly associated with a higher recurrence rate (p = 0.015), a shorter disease-free survival (p = 0.014), advanced (IIIB) clinical stage (p = 0.034), and almost significantly with total survival (p = 0.055). In a multivariate Cox regression analysis, a high SPF in diploid tumors retained its independent prognostic power, being significantly associated with a shorter disease-free survival (p = 0.00049) and total survival (p = 0.0077). It also allowed to identify a subgroup with an ominous prognosis among patients < or = 50 years of age with early stage tumors. Our results fully validate the recommendations of the 1992 Maine Consensus Meeting.