Receptors - Their prognostic and predictive value

Estrogen and progesterone receptors (ER and PgR) have now been studied in clinical breast cancer for more than 25 years. Positive receptor status correlates with favorable prognostic features, including a lower rate of cell proliferation and histological 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 the overall prognostic significance of receptor status is modest. These data suggest that ER status does not correlate with the affinity of a tumor to metastasize but may correlate with the time required for metastases to become clinically evident. ER and PgR have the greatest use in predicting response to hormonal therapy both in the adjuvant setting and for advanced disease. When the assay is done stringently and the cutoffs for ER negativity and positivity are defined by clinical studies, receptor status is helpful in identifying groups of patients who are very unlikely to benefit from hormonal therapy. Tumors that express both ER and PgR have the greatest benefit from hormonal therapy, but those containing only ER or only PgR still have significant responses. Understanding receptor biology may further help to improve the predictive ability of receptor status in the future. ER and PgR variants and isoforms may have different functions that may contribute to hormone sensitivity or resistance. Expression of receptor-interacting proteins, which can modulate transcriptional activity, may also prove to be important in determining responsiveness to endocrine therapy. In summary, ER and PgR are important biological markers that assist physicians in individualizing and selecting appropriate therapy for patients with breast cancer. Copyright (C) 2000 by W.B. Saunders Company.