We set out to define the molecular mechanisms underlying anti-estrogen resistance and this provided a collection of BCAR genes which are representative of the escape pathways that these breast cancer cells take in our laboratory studies, said the studys lead investigator, Lambert Dorssers, Ph.D., a cell biologist at the Department of Pathology of the Erasmus Medical Center, in Rotterdam.
We have also shown that the majority of the BCAR genes identified are linked to clinical breast cancer, suggesting that their signaling pathways contribute to the progression of breast cancer and to tamoxifen therapy resistance, he said.
Using the functional screen, the investigators looked at surgically removed primary tumors from 413 patients who had not yet received systemic therapy and found three genes AKT2, EGFR, and TRERF1 that were independently associated with tumor aggressiveness.
In other studies of breast tumor samples from recurrent patients treated with tamoxifen, they had found five genes BCAR3, ERBB2, GRB7, TLE3, and TRERF1 that were associated with progression-free survival, depending on the level of their expression. Some of these genes were confirmed by the current study. For example, we found that high levels of GRB7 are associated with a quicker relapse, Dorssers said.
The researchers are now defining how these genes function within breast cancer cells in order to pinpoint possible targets for treatment. Expression of the genes could also be used to classify patients for more intensive or alternative adjuvant treatment, or to suggest specific treatments in the advanced state of ER-positive disease, he said.
Response to preventive HER2/neu peptide (E75) vaccine based on HER2/neu status: Abstract 2545
A HER2 peptide E75 vaccine reduced mortality in patients with HER2-positive brea
|Contact: Staci Vernick Goldberg|
American Association for Cancer Research