Proliferative index of breast carcinoma by thymidine labeling: prognostic power independent of stage, estrogen and progesterone receptors

Abstract

We studied cellular proliferation by measuring the tritiated thymidine labeling index (TLI) in slices of primary invasive breast carcinomas. Estrogen receptor (ER) and progesterone receptor (PgR) were measured by ligand-binding assay. The TLI was a strong independent predictor of survival and relapse-free survival in women with or without axillary lymph nodal metastases and in American Joint Committee stage I. In operable node-negative women treated surgically, predicted survival at 5 years was 89 +/- 4% (probability +/- standard error) for 81 patients with low TLI (less than or equal to 3%), 64 +/- 7% for 101 with mid TLI (3.1-8%), and 66 +/- 6% for 86 with high TLI (greater than 8%) (P = 0.001). Probabilities of survival for patients with positive axillary nodes were 79 +/- 6% for 86 with low, 71 +/- 7% for 71 with mid, and 52 +/- 6% for 89 with high TLI (P = 0.0002). In stage I patients (tumor diameter not exceeding 2 cm), 5-year survival probabilities were 93 +/- 4% in 70 with low, 72 +/- 8% in 43 with mid, and 58 +/- 10% in 35 with high TLI, (P = 0.0005). The TLI was predictive for survival and relapse-free survival within subgroups positive and negative for ER and positive for PgR (P less than 0.05) in stage I patients, and a predictive trend was observed in the PgR-negative subgroup (P = 0.16). TLI also predicted within different categories of vascular invasion and nuclear grade. A stepwise Cox proportional hazards model selected TLI, number of positive axillary lymph nodes, and maximum diameter of the breast carcinoma as independent variables predictive of relapse, and added ER as a fourth variable for prediction of survival.