Cell kinetics in selection and stratification of patients for adjuvant therapy of breast carcinoma.

Pulse in vitro thymidine labeling index (TLI) was used to measure proliferative activity in 757 infiltrative breast carcinomas. The TLI varied from 0.00% to 35.6%, and the frequency distribution was positively skewed, with a mean of 7.1% and a median of 5.2%. The TLI was negatively correlated with the age of the patient and content of estrogen and progesterone receptors and was positively correlated with the size of the carcinoma and the degrees of nuclear anaplasia, necrosis, and inflammatory cellular infiltrate. The TLI did not correlate with the number of axillary lymph node metastases. The TLI of locally advanced carcinomas were elevated significantly. Evaluation of the clinical course in a series of 278 patients showed that the TLI is a prognostic indicator independent of stage and estrogen receptor content. Patients with negative axillary lymph nodes who had TLI above the median had more than twice the probability of relapse within 4 years as patients with TLI below the median. Similar results have been reported by Silvestrini et al. The TLI can be used to select and identify high-risk patients and to stratify patients for trials of adjuvant therapy. The DNA index and the percent of nuclei with S-phase DNA content estimated by flow cytometry hold promise as prognostic indicators but have not been as well studied as the TLI.