New hope for estrogen-resistant breast cancer
A specific change that occurs when breast cancer tumors become resistant to antiestrogen therapy might make the tumors susceptible to treatment with chemotherapy drugs, according to a new finding.
Estrogen-receptor positive breast cancer represents about 70% of breast cancer cases, and most patients respond well to antiestrogen therapies, at least for a few years. Therapeutic strategies for estrogen-receptor positive breast cancer include blocking the body's production of estrogen with aromatase inhibitors, preventing estrogen from binding to the estrogen receptor by binding to the drug tamoxifen instead, and destroying the estrogen receptor completely. However, 50% of patients with estrogen-receptor positive breast cancer will relapse and eventually die from the disease within 15 years.
Andrew Stone, PhD, of the Garvan Institute in Sydney, Australia, led a research team that demonstrated that the BCL-2 gene becomes epigenetically silenced in resistant tumors. Their study, published in Molecular Cancer Therapeutics (2013; doi:10.1158/1535-7163.MCT-13-0012), shows that the silencing of BCL-2 in human disease and several different cell models occurs through DNA methylation. This process is potentially detectable in the blood, which could provide a diagnostic marker.
“The main purpose of the BCL-2 gene is to keep cells alive, so when the gene is silenced, cells become more vulnerable to chemotherapy,” said Stone. “The next step will be to test our findings in clinical studies. We propose that if the BCL-2 gene is silenced, patients with estrogen-receptor positive breast cancer would benefit from combination therapy. In other words, tamoxifen could be used in combination with a chemotherapy drug to kill off vulnerable tumor cells.”
Stone went on to explain that technology now exists to profile the methylation of BCL-2 in all patients, whether estrogen-responsive or estrogen-resistant. Also, the proposed chemotherapy drugs for the trials based on detecting the methylation of BCL-2 are already in use.