CELL-PROLIFERATION IN 3.800 NODE-NEGATIVE BREAST CANCERS - CONSISTENCY OVER TIME OF BIOLOGICAL AND CLINICAL INFORMATION PROVIDED BY H-3 THYMIDINE LABELING INDEX

For breast cancer, many prognostic markers that initially appeared pro mising have failed to maintain their clinical predictive value. Few re ports have analyzed the consistency over time of biological and clinic al information provided by biomarkers. Tumour cell proliferation has a cquired relevance as an indicator of prognosis and of response to trea tment. Since its clinical role has been investigated for some decades, cell proliferation represents an ideal marker for an over-time valida tion. In 3,800 node-negative breast cancers recruited between 1972 and 1991, the consistency of information provided by the H-3-thymidine la belling index (TLI), in terms of basic relations with other clinico-pa thological and biological variables and clinical predictivity, was eva luated using a combined analysis of results previously published by ou r group for distinct series of patients. Clinical predictivity was ana lyzed on a subset of 2,067 patients given local regional therapy until relapse and followed for a median time from 6 to 10 years. Over the e ntire period TLI maintained a weak direct relation with tumour size an d an inverse strong relation with steroid receptors. An increase in TL I was observed for tumours in post-menopausal patients up to the mid 1 980s, During 3 different accrual periods (1972-1983; 1984-1987; 1988-1 991), TLI was a consistent and independent predictor of relapse-free t ime, distant metastasis and overall survival, regardless of its consid eration as a continuous variable or with a cutoff value of 3%. The rep roducibility of our results over time provides support to the consiste ncy of the methodology used and of the biological and clinical informa tion obtained when using TLI as an indicator of breast cancer cell pro liferation. (C) 1997 Wiley-Liss, Inc,.