Estrogen receptor beta--an independent prognostic marker in estrogen receptor alpha and progesterone receptor-positive breast cancer?

Both subtypes of estrogen receptor (ER), ERalpha and ERbeta, are normally present in the mammary gland. The role of ERalpha as a prognostic marker in breast cancer is well established due to the beneficial effect of providing tamoxifen as adjuvant therapy. The role of ERbeta, however, is less clear. To gain insight into the importance of ERbeta in breast cancer, 145 primary breast cancers were examined by immunohistochemistry for ERbeta, and the expression level was compared with ERalpha and progesterone receptor (PR) status. Especially, we wanted to examine the significance of ERbeta in the contrasting ERalpha+/PR+ and ERalpha-/PR- subgroups. In the ERalpha+/PR+ subgroup (dual positive), the survival difference between patients with low, medium and high ER beta level was statistically significant (p = 0.004), with more than 70% of patients with medium and high ERbeta levels surviving 100 months, compared with less than 30% in the group with low ERbeta level. Further, for ERalpha+/PR+ patients there was a reduced risk of fatal outcome by multivariate analysis with increasing ERbeta levels (p(trend) < 0.01 [univariate analysis]; p(trend) = 0.05 [multivariate analysis]). The risk was 31% and 27% for medium and high ERbeta levels, respectively, compared with low ERbeta level, adjusting for standard prognostic factors such as tumor diameter, nuclear tumor grade (quantified by mean nuclear area), lymph node status, and patient age at operation. For patients with ERalpha-/PR- tumors (dual negative), however, there was no association between ERbeta levels and patient outcome. Our findings indicate that ERbeta expression provides independent prognostic information for breast cancers with ERalpha/PR-positive status, a feature typical among screen-detected breast cancers. The role of ERbeta needs to be further evaluated especially in this group of breast cancers.