Estrogen and Progesterone Receptor Determinations in Breast Cancer—Technology, Biology and Clinical Significance

Our present state of knowledge regarding estrogen and progesterone receptors (ER and PgR) has led to changes in. treatment strategies: patients without receptors in their tumor tissues cannot be expected to respond to endocrine therapy. Furthermore, groups of patients with specifically good or poor prognoses can be selected. Treatment of the disease now approaches being of a rational rather than of an empirical nature. However, it is imperative that we achieve a considerably higher level of understanding before we can predict, with high probabilities, which patients will benefit from endocrine therapy. Only through a coordinated effort by many centers can we hope to attain this goal. In such collaborations there are several factors that must be taken into consideration if reproducible conclusions are to be reached: a) sampling of the tumor biopsy for analysis, b) potential differences in assay procedures which may affect results, and c) the composition of the population studied. Since the traditionally used ligand binding assay (dextran-coated charcoal (DCC) method) is highly sensitive even to slight modifications in assay procedure, intra-and interlaboratory standardization of receptor analyses is challenging. Accordingly, correlations between receptor status and/or concentrations and the clinical course of the disease from different centers often demonstrate discrepant results. With the greater reproducibility and sensitivity of the newly developed immunoenzymometric assay (IEMA) methods, many of these problems might be solved in the future and inter-center clinical studies will thus be facilitated.In the national Danish Breast Cancer Cooperative Group (DBCG) project, approximately 90% of all patients with primary breast cancer are registered. Estrogen and progesterone receptor (ER and PgR) determinations have been performed on tumor tissue from approximately 30% of these patients in one single laboratory. The results of these analyses are presented here for approximately 4000 patients in relation to age, menopausal status, tumor size, grade of anaplasia, and lymph node involvement.Biologically and clinically there appear to be three fundamental types of tumor tissues; hormone responsive (ER+PgR+ and ER-PgR+), hormone non-responsive (ER-PgR-), and tissues of a more dubious hormone responsive nature (ER+PgR-), which occur predominantly among postmenopausal patients. Several lines of evidence indicate that among the postmenopausal patients there may be an estrogen bidning molecule similar to but distinct from the normal, physiologically functioning ER molecule.Around 30% of the patients have been in DBCG protocols where no adjuvant systemic therapy has been administered. Due to this large number of cases, the recurrence-free survival (RFS) of the not adjuvantly treated disease in relation to receptor status can be reliably analyzed. Both ER and PgR statuses were found to be significant prognostic variables for premenopausal women under 50 years of age. In contrast, in the postmenopausal women, neither receptor status was found to be a significant prognostic factor in the low risk group, (tumor < 5 cm, no lymph node involvement). In high risk, postmenopausal women, however, ER status was a significant prognosticator for RFS; moreover, it appeared to be independent of lymph node status.While ER and PgR are gaining wide acceptance as significant prognostic factors in the treatment of breast cancer, other prognostic factors must be found in order to stage patients as accurately as possible at the time of the primary surgery so that the appropriate adjuvant treatment can be given to those patients at high risk of recurrent disease, and thus improve survival in breast cancer.