Tamoxifen promotes metastasis in some breast cancer cells
Tamoxifen works by blocking estrogen in the breast tissue by attaching to the estrogen receptors in breast cells. Studies show that tamoxifen promotes metastasis in some breast cancer cells. The drug has been used as a first-line endocrine treatment for breast cancer for decades.
In 2008 researchers in UK found that some women develop resistance to the drug. Dr Jason Carroll, the lead researcher and author of the paper published in the medical journal Nature said “We have discovered that for tamoxifen to work it has to block the gene ErbB2 and it does this by using a control switch that is hidden in the background of the genome, within the ErbB2 gene itself. In order for tamoxifen to be effective, this switch must be held in the off position by Pax2. Now we understand how women can develop tamoxifen resistance.”
The ERα66 estrogen receptor is the main molecular target for tamoxifen treatment. However, many patients develop resistance with unclear mechanisms. Lead by Qiang Wang a large cohort study of breast cancer patients who underwent surgery, followed by tamoxifen treatment, researchers showed that ERα36, a variant of ERα66, correlates with poor prognosis.
The future of treatment
Until now, ERα66 has been the only clinically used biomarker for the selection of tamoxifen therapy. However, little is actually known about the role of ERα36, in tamoxifen resistance of breast cancer. While the benefit of survival has been observed in patients receiving tamoxifen some patients have developed tamoxifen resistance and cancer metastasis.
This study not only reveals ERα36 as a marker for endocrine therapy but also provides a promising therapy path for women who develop tamoxifen-resistant breast cancer.
You can read the study here.