More than 10 years have passed since the discovery of the second
estrogen receptor,
estrogen receptor beta (
ERbeta). It is now evident that
ERalpha is not the only ER in
breast cancer cells; in fact,
ERbeta is expressed in the majority of breast
cancers although at lower levels than in the normal breast. In addition,
ERbeta is expressed in
breast cancer infiltrating lymphocytes, fibroblasts and endothelial cells, all known to influence
tumor growth. By overexpressing or knocking-out
ERbeta in
breast cancer cell lines, several researchers have investigated its function with respect to proliferation and
tumor growth. It appears that
ERbeta is anti-proliferative, in many ways antagonising the function of
ERalpha. Furthermore,
phytoestrogens have a binding-preference for
ERbeta and several epidemiological studies indicate a
breast cancer preventing effect of this class of compounds.
Tamoxifen is one of the standard, adjuvant treatments for
ERalpha positive
breast cancer, classically thought to mediate its effect through
ERalpha. However, in several recent studies,
ERbeta has been described as a potential marker for
tamoxifen response. In summary, experimental, epidemiological as well as diagnostic studies point towards
ERbeta as an important factor in
breast cancer, opening up the possibility for novel
ERbeta-selective
therapies in the treatment of
breast cancer.