Steroid hormone receptors in breast cancer management

Estrogen and progesterone receptors (ER and PR) have now been studied in clinical breast cancer for more than 20 years. Positive receptor status correlates with favorable prognostic features including a lower rate of cell proliferation and histologic evidence of tumor differentiation. During the first several years after diagnosis, patients with ER-positive tumors tend to have a lower recurrence rate; however, this is balanced by a higher recurrence rate in subsequent years so that the overall prognostic significance of receptor status is modest. ER and PR have their greatest utility in predicting response to hormonal therapy, both in the adjuvant setting and for advanced disease. When the assay is done properly and cut-offs for ER-negativity and positivity are defined by clinical studies of patients treated with endocrine therapy, receptor status is very helpful in identifying groups of patients who are very unlikely to benefit from hormonal therapy. Tumors that express both ER and PR have the greatest benefit from hormonal therapy, but those containing only ER or only PR still have significant responses. Two types of estrogen receptors, ER alpha and ER beta, have now been identified. Although there is considerable homology between these receptor forms, they appear to have important structural and functional differences that may be important for tissue and promoter-specific regulation of gene expression. These receptor forms, as well as ER variants and mutants, may also contribute to hormonal sensitivity and resistance. PR also exists in two forms, PRA and PRE. PRA appears to have repressor functions on both PRE and ER alpha, and the ratio of PRA to PRE in clinical breast tumors needs to be studied for its possible clinical relevance. Expression of receptor-interacting proteins can also modulate ER transcriptional activity, and these too need additional study to determine if they are markers of hormonal sensitivity or resistance. In summary, ER and PR status are important biomarkers that help physicians individualize therapy.