Subpopulations of breast carcinoma defined by S-phase fraction, morphology, and estrogen receptor content

The S-phase fraction (SPF), defined as the number of cells per hundred that showed evidence of nuclear DNA synthesis detectable by autoradiography after in vitro incubation with tritiated thymidine, was measured in 170 primary, invasive carcinomas of the breast. Assay for estrogen receptor was performed on tissue from 129 carcinomas, and 34 were also assayed for progesterone receptor. The concentration of estradiol-17 beta was measured in the serum of 69 patients. All carcinomas were analyzed for a variety of histologic features and were classified into morphologic types. SPF were lognormally distributed and were negatively correlated with the patient's age and presence of estrogen receptor, but not with presence of progesterone receptor, size of the carcinoma, number of axillary nodal metastases, or concentration of estradiol-17 beta in serum. The SPFs of lobular, mucinous, and tubular carcinomas were consistently low (geometric mean 1.2, range 0.05 to 3.55), and the SPFs of medullary and atypical medullary carcinomas were consistently high (geometric mean 14.0, range 7.77 to 20.2), whereas carcinomas of other types (not otherwise specified) had an intermediate geometric mean (4.7) and a broad range (0.09 to 25.4). The carcinomas that were not otherwise specified could be divided into three groups with different geometric mean SPFs by nuclear morphologic criteria (1.2 for minimal atypicality, 3.5 for moderate, and 7.9 for severe). Therefore it is possible to sort breast carcinomas histologically into groups with low, intermediate, and high SPF. Correlations between SPF, estrogen receptor content, and microscopic morphology indicate the existence of distinctive subpopulations of breast carcinoma that may have epidemiologic and therapeutic importance.