Clinical significance of the expression of estrogen receptors α and β for endocrine therapy of breast cancer

The assessment of the estrogen receptor (ER) α and the progesterone receptor (PgR) in breast cancer tissues is important for discriminating between hormone-dependent and hormone-independent tumors. ERβ, a more recently discovered ER, may influence estrogen action through the ERα pathway. To evaluate the clinical significance of these receptors in the response to endocrine therapy, we investigated their expression in primary breast cancer tissues. ERα and PgR were evaluated using immunohistochemistry (IHC) and enzyme immunoassay (EIA) and ERβ expression was determined using IHC and reverse transcription-polymerase chain reaction. When the cut-off level of EIA was set at 13 fmol/mg protein for ERα and that for IHC was set as an IHC score between 2 and 3, a significant correlation between ERα EIA and IHC was seen (concordance rate 88.4%). This indicates that this cut-off level of ERα IHC can be adopted to quantify breast cancer prognoses. Furthermore, the tumors with positive expression of ERα IHC or PgR IHC using this criterion were significantly related to the response to endocrine therapy. Additionally, tumors with positive expression of ERβ wild-type tended to have a better response to endocrine therapy than negative ones, and tamoxifen responders tended to exhibit a lower ratio of ERβcx (one of the ERβ variants) to ERβ wild-type than nonresponders. The results concerning ERβ are not yet fully understood; further investigations and evaluations should analyze the role of ERβ wild-type and variant type in breast cancer treatment.