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In vitro influence of estradiol or progesterone on the thymidine labeling indices of human benign breast tumors.

Using an in vitro tritiated thymidine (3H-dThd) nuclear labeling followed by autoradiography, the effects of 17-beta-estradiol (E2) or progesterone (Pg) on cell proliferation were studied in 22 human benign breast tumors, i.e. 7 fibroadenomas 8 fibrocystic dysplasias 4 gynecomastias and 3 phyllodas. Small tumor fragments were incubated in a chemically-defined medium without serum and were hormonally stimulated in vitro. The procedure used allowed discrimination between weak labeling, suggestive of DNA repair mechanism, and strong labelling, suggesting a true DNA synthesis (S phase). Taking this into account, our results have shown that both estradiol and progesterone can induce in vitro cell replication of both ER+PgR+ and ER-PgR- human breast fibroadenoma, without affecting those of fibrocystic dysplasia, gynecomastia and phylloda. Progesterone, but not estradiol, might significantly decrease DNA repair mechanism in fibrocystic dysplasia, according to the Pg-induced decrease of nuclear incorporation of small amounts of 3H-dThd. We have thus characterized a dynamic test of hormone dependence which permits in vitro study of the hormonal sensitivity of human benign breast tumors, as well as that of any other human neoplasm. This test could be of great value to help clinicians to diagnose and treat hormone-dependent neoplasms properly. Its clinical relevance is now under study.