期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：5
页码：1933-1938
DOI：10.1073/pnas.1323719111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The role of estrogen receptor (ER) as a target in treatment of breast cancer is clear, but those of ER{beta}1 and ER{beta}2 in the breast remain unclear. We have examined expression of all three receptors in surgically excised breast samples from two archives: (i): 187 invasive ductal breast cancer from a Japanese study; and (ii) 20 lobular and 24 ductal cancers from the Imperial College. Samples contained normal areas, areas of hyperplasia, and in situ and invasive cancer. In the normal areas, ER was expressed in not more than 10% of epithelium, whereas approximately 80% of epithelial cells expressed ER{beta}. We found that whereas ductal cancer is a highly proliferative, ER-positive, ER{beta}-negative disease, lobular cancer expresses both ER and ER{beta} but with very few Ki67-positive cells. ER{beta}2 was expressed in 32% of the ductal cancers, of which 83% were postmenopausal. In all ER{beta}2-positive cancers the interductal space was filled with dense collagen, and cell nuclei expressed hypoxia-inducible factor 1. ER{beta}2 expression was not confined to malignant cells but was strong in stromal, immune, and endothelial cells. In most of the high-grade invasive ductal cancers neither ER nor ER{beta} was expressed, but in the high-grade lobular cancer ER{beta} was lost and ER and Ki67 expression were abundant. The data show a clear difference in ER expression between lobular and ductal breast cancer and suggest (i) that tamoxifen may be more effective in late than in early lobular cancer and (ii) a potential role for ER{beta} agonists in preventing in situ ductal cancers from becoming invasive.
