Differences in estrogen receptor alpha variant messenger RNAs between normal human breast tissue and primary breast carcinomas

We evaluated the differences in prevalence and functional activity of human estrogen receptor alpha (hER) variant mRNA between 21 normal breast tissues and 41 primary breast carcinomas using a functional assay in yeast for the hER First, we found that the presence of wild-type hER, relative to the total amount of hER, differs markedly (P < 0.0001) between normal breast tissue (median, 85% wild-type hER) and breast tumors (median, 74% wild-type hER). Second, the hER variants with altered function that are present in normal breast tissue are mainly one-exon deleted splicing variants (median, 100%), whereas in breast tumors only half of all variants lack just one single exon (median, 50%; P < 0.0001). Our results suggest that hER-dependent estrogen responsiveness of breast tissue may change during tumor outgrowth, indicating that specific hER variants may play a role in breast cancer development or progression.