Preservation of Steroid Hormone Receptors in Organ Cultures of Human Breast Carcinomas

In a study of human breast carcinomas in short-term organ culture, in which plasminogen activator modulation by estrogen was used as a test of estrogen sensitivity (R. Mira-y-Lopez and L. Ossowski, Cancer Res., 47: 3558–3564, 1987), we found that the number of estrogen and progesterone receptor-positive cancers showing estrogen sensitivity was less than anticipated from reported rates of antiestrogen-induced clinical remission. Since in these experiments the estrogen receptor (ER) content of the tumor cultures was only inferred from determinations carried out before culture, we postulated that the apparent estrogen insensitivity of some tumors resulted from poor ER preservation. We have now measured ER levels directly in cultured tissue and found that (a) ER levels in slices of human breast cancers decreased 78% (median) after 1–4 days; 4 of 16 (25%) ER-positive breast cancers had no detectable estradiol binding activity after culture; (A) the drop in ER level was a result of net receptor loss rather than inactivation of binding activity; (c) loss of cell viability could be definitively ruled out as a cause of decreased receptor level; (d) Cortisol receptor levels in human breast cancers and ER levels in other hormone-responsive cancers also decreased in culture, and to a similar extent. Higher ER levels (sometimes equal to preculture levels) were preserved by culture at subphysiological temperature or in slices of controlled thickness, not exceeding 0.6 mm. These findings should be considered when organ culture is used to predict tumor hormone responsiveness.