Immunological quantitation of nuclear receptors in human breast cancer: relation to cytosolic estrogen and progesterone receptors.

Nuclear estrogen receptors (ERn) can now be reliably analyzed using the monoclonal estrogen receptor enzyme immunoassay. In a consecutive series of 135 breast cancer biopsies, ERn as well as cytosolic estrogen receptor (ERc) and progesterone receptor (PgR) concentrations were determined to evaluate whether ERn assays provide additional valuable information for the clinical management of the disease. Furthermore, by performing analyses on this relatively large number of patients, we sought explanations for the occurrence of the receptor profiles of ERc negative PgR positive and ERc positive PgR negative, which are found in a significant proportion of tumor biopsies. Eight-four % of all tumors are classified as ERn positive (greater than or equal to 10 fmol/mg nuclear extract protein) using the monoclonal assay technique. Two trends are evident: ERc positivity was found to be associated with ERn positivity (greater than or equal to 10 fmol/mg cytosol protein) in 98% of the cases investigated; and PgR positivity (greater than or equal to 10 fmol/mg cytosol protein) was found to be associated with ERn positivity in 95% of the cases investigated. However, a major proportion (approximately 28%) of ERn positive tumors are either ERc negative or PgR negative. The pattern of ERc negative ERn positive occurs almost exclusively among younger women, most of whom also had detectable amounts of PgR in their tumor tissues, while the pattern of ERn positive PgR negative occurs primarily among older women. ERn concentration was found to be significantly correlated to the concentration of both PgR and ERc. While the correlation between ERn and PgR was found to be strongest among women younger than 50 years of age, the correlation between ERn and ERc was strongest among women older than 50 years. Young women were found to have a significantly higher proportion of total tissue estrogen receptor present as ERn than older women (27 versus 14%). The information obtained by performing ERn analyses concurrently with or in place of ERc and PgR analyses does not appear to be valuable for the clinical management of the disease. However, this new method for determination of ERn is a significant advance in receptor technology that permits reevaluation of established enigmas concerning the biology and natural history of breast cancer.