Influence of steroid hormones on the growth fraction of human breast carcinomas.

Abstract

The growth fraction (GF) of human breast adenocarcinomas was studied in order to determine whether it was influenced by certain biologic characteristics of the host and whether it was modulated by the tumor's steroid hormone receptor status. It was also examined whether steroid treatment in vitro stimulated tumor's GF. Thirty-five primary breast adenocarcinomas from patients ranging in age from 26 to 85 years were analyzed for size and estrogen receptor (E2R) and progesterone receptor (PR) status. One portion of each tumor was cultured in medium 199 under four different conditions: addition of insulin alone or with 17 beta-estradiol (E), progesterone (P), or a combination of both hormones (E + P). In six cases, a dose-response curve was established for E (10(-14) to 10(-12) mol/L) and P (10(-11) to 10(-9) mol/L). Tissues were exposed to a continuous pulse of 2.5 microCi/mL (3H)-thymidine for five days before fixation and processing for autoradiography. GF ranged from 0.0074 to 0.3852, median 0.0550, and it was arbitrarily classified as low GF, less than 0.0550; or high GF, equal or greater than 0.0550. GF was significantly higher in patients with lymph nodes free of metastatic tumor than in those with positive lymph nodes. Estradiol treatment at low doses increased GF in 40% of tumors, whereas high doses increased GF in 14%. Progesterone treatment increased GF in 30% of tumors treated with low doses and in 14% of those treated with high doses. Treatment with E + P markedly depressed the GF of 85% of the tumors. It was concluded that the GF of breast carcinomas showed a great variability, which seemed to be independent of host factors such as age, menopausal status, parity history, or smoking habits; a second conclusion was that breast tumors' GF was not stimulated by steroid hormone treatment in vitro, and its response did not correlate with their hormone receptor status.