Tamoxifen is one of the most effective treatments for
breast cancer. Standard practice is to select patients who are likely to respond to this therapy through the evaluation of
estrogen receptor (ER) and
progesterone receptor (PR) in the primary
tumor tissue. Over the past 25 yr that physicians have been using ER determination to guide
tamoxifen use, numerous studies have demonstrated that this molecular marker is useful in predicting benefit from
tamoxifen. ER has been analyzed for many years using ligand-binding assays. However, current practice involves the use of immunohistochemical-based assays to detect
ERalpha Immunohistochemistry (IHC) has several advantages. For example, IHC evaluates
tumor cell heterogeneity, can be used to study small samples, is less expensive, and allows direct correlation with multiple histopathological
tumor features and other molecular markers. PR, an
estrogen-responsive protein, can also be useful in predicting response to
tamoxifen in specific clinical situations. In recent years, several other markers of
tamoxifen response have been examined, including: pS2 (another
estrogen-regulated protein),
heat-shock proteins 27 and 70, bcl-2 protein, c-erbB-2 (HER-2/neu) oncoprotein, and mutated
p53 tumor suppressor protein. In this article, we present an analysis of the data on these new molecular markers. Overall, from numerous studies, the data indicate that in addition to
ERalpha bcl-2 is a potential candidate to help further improve our ability to predict response to
tamoxifen. ER and bcl-2 are the most useful molecular markers to better identify
breast cancer patients who will respond to
tamoxifen and who will have prolonged survival.