Breast carcinoma cell kinetics, morphology, stage, and host characteristics. A thymidine labeling study

The thymidine labeling index (TLI) was measured in 757 primary, invasive breast carcinomas in women by an in vitro method that achieved intense labeling of S-phase cells. The frequency distribution of the TLI was positively skewed but could be normalized by taking logarithms. The mode was 2%; median, 5.2%; geometric mean, 4.5%; mean 7.1%. The TLI was significantly related to a number of pathological features. Carcinomas of large size, with inflammatory or otherwise locally aggressive, undifferentiated histologic and nuclear characteristics, necrosis, inflammatory cellular response, and circumscribed tumor border showed strong tendencies to have high TLIs. The TLI was not significantly related to race, axillary lymph nodal status, or invasion of lymphatics and blood vessels. Breast carcinomas replicated cells at high rates ("rapid growth") more often in young women than in aged women. Lack of either estrogen receptor (ER) or progesterone receptor (PgR) was associated with high TLI. Although the inverse relationship between TLI and PgR was more or less linear, and the relationship between TLI and ER was not, differences in TLI between PgR-negative and PgR-positive patients were no greater than between ER-negative and ER-positive tumors. The degree of inflammatory infiltrate was strongly related to both proliferative rate and evidence of cell-death, indicative of a secondary phenomenon rather than a role in regulation of tumor growth. The proliferative rate of breast carcinoma appears to be an important determinant of morphologic patterns. Although it modulates the pace of progress of the disease, it is at most a weak determinant of metastasis.