Abstract
In this single-centre study of 881 patients, S-phase fraction (SPF) was shown to be a significant prognostic marker in terms of overall survival (OS), relapse-free survival (RFS) and survival after relapse (SAR). Further, SPF had independent prognostic significance when considering a range of other clinicopathological variables, namely tumour grade and stage, nodal status, patient age, tumour size, menstrual status and treatment details. For OS and RFS, SPF was the second strongest predictor of the clinical course of the disease after nodal status, and for SAR it was the strongest prognostic marker. SPF correlated positively with histological grade but was the stronger predictor of survival. The distribution of SPF values was markedly different for the two ploidy classes of tumour, with DNA aneuploid tumours having a significantly higher average SPF. However, SPF retained its independent prognostic ability when DNA diploid and aneuploid tumours were analysed separately, DNA ploidy itself also proved to be an independent prognostic marker but the survival difference between the two ploidy classes was much less than that seen for different levels of SPF. Tumours with several DNA aneuploid populations (multiploid tumours) tended to have a worse prognosis than other aneuploid tumours but this trend did not reach statistical significance. In this and other studies from this centre, SPF has proved to be a robust predictor of clinical outcome in carcinoma of the breast.
Highlights
With complete data on 881 patients we have investigated the relationship of flow cytonmtric parameters to overall survival (OS), relapsefree survival (RFS), survival after relapse (SAR) and the clinicopathological variables listed below
Selection of cases for S-phase fraction (SPF)/ploidy analyses All the patients in this study presented at the ICRF Breast Unit at Guy's Hospital between 1975 and 1991
Relapse-free survival Table III shows univariate and multivariate relapse-free survival results. These are very similar to the survival results, though adjuvant chemotherapy and adjuvant tamoxifen both show much greater significance
Summary
Sampl preparation Two 50-pm sections were obtained from routinely fixed, paraffin-embedded tissue blocks for each case. SPF was calculated for aneupoid cells only in the case of DNA aneuploid tumours. Multiploid tumours did not exhibit significantly worse survival than diploid/aneuploid tumours Survival and relapse-free survival were calculated by the method of Kaplan and Meier (1958), with significance being cases, the remaining analyses concern the 802 diploid and aneuploid cases. This allows calculation of univariate P-values on continuous variables The Mann-Whitney test was used to evaluate the significance of the difference in SPF values between aneuploid and diploid cases. Histological grade, SPF, menstrual status, tumour size, nodal status and number of nodes involved, ploidy and adjuvant chemotherapy were all significant as indicators of prognosis.
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