Cell proliferation in 3,800 node-negative breast cancers: Concistency over time of biological and clinical information provided by3H-Thymidine labelling index

Abstract

For breast cancer, many prognostic markers that initially appeared promising have failed to maintain their clinical predictive value. Few reports have analyzed the consistency over time of biological and clinical information provided by biomarkers. Tumour cell proliferation has acquired relevance as an indicator of prognosis and of response to treatment. Since its clinical role has been investigated for some decades, cell proliferation represents an ideal marker for an over-time validation. In 3,800 node-negative breast cancers recruited between 1972 and 1991, the consistency of information provided by the 3 H-thymidine labelling index (TLI), in terms of basic relations with other clinico-pathological and biological variables and clinical predictivity, was evaluated using a combined analysis of results previously published by our group for distinct series of patients. Clinical predictivity was analyzed 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 entire period TLI maintained a weak direct relation with tumour size and an inverse strong relation with steroid receptors. An increase in TLI was observed for tumours in post-menopausal patients up to the mid 1980s. During 3 different accrual periods (1972-1983; 1984-1987; 1988-1991

Molecular markers in clinical radiation oncology

“…We will not extensively review this topic, and the reader is referred to numerous reports and reviews of these proliferative markers as predictors of radiation response in the literature Begg, 1995;Gasparini et al, 1995;Ciancio et al, 1997;Silvestrini et al, 1997a;Wilson, 1998;Begg et al, 1999;Bradford, 1999;Danic et al, 1999;Bjork-Eriksson et al, 2000;Corvo et al, 2000;Silvestrini, 2000;Sittel et al, 2000). There are conflicting reports regarding the majority of proliferative markers with respect to radiation sensitivity and local control with radiation therapy.…”

Cell Cycle Phase-Specific CHemotherapy: Computation Methods for Guiding Treatment

“…Empirically, aspects of cell kinetics, for example, the quiescent fraction, the S-phase fraction, and apoptotic rates, substantially influence prognosis and response to treatment. [12][13][14][15][16][17] The timing of drug delivery, drug pharmacokinetics, and drug pharmacodynamics may interact in complex ways that can best be understood and predicted with the aid of a model. Individual variation in cell kinetics, drug resistance, and drug metabolism further complicates the task of optimizing drug doses, schedules, and combinations in a given patient.…”

Cell proliferation and outcome following doxorubicin plus CMF regimens in node‐positive breast cancer

“…Immediately after surgery, part of the tumour material was incubated with [ 3 H]thymidine and then processed for conventional histoautoradiographic procedures for the determination of TLI (Silvestrini et al, 1997a). The rest of the tumour material was frozen in liquid nitrogen and stored at -80°C for ER determination (Silvestrini et al, 1996a).…”

“…Samples were incubated for 1 hr in [ 3 H]thymidine with a proliferation kit (Euroframe, Asti, Italy) and processed for autoradiography as previously described (Silvestrini et al, 1997a). TLI was evaluated independently by 2 observers at the time of initial diagnosis by scoring a total of Ͼ3,000 cells on consecutive areas of the same tumour lesion and defined as the percentage ratio between labelled cells and total number of tumour cells.…”