Estrogen May Trigger Brain Metastasis in Triple-negative Breast Cancer, Study Shows

Estrogen May Trigger Brain Metastasis in Triple-negative Breast Cancer, Study Shows
Estradiol, a type of estrogen and the major female hormone, may drive the spread of cancer to the brain in women with triple-negative breast cancer (TNBC), a study in mice and human cells reports. Researchers identified a chain of molecular events triggered by estradiol that appears to be behind tumor cells' ability to form brain metastases. This process involves increased production of a brain-specific protein called BDNF and the activation of its receptor molecule, TrkB, in tumor cells. This discovery may have important therapeutic implications, since it provides a basis to use estradiol-depletion treatments or inhibitors that target this pathway to prevent or delay the spread of TNBC to the brain. The study, “Estradiol induces BDNF/TrkB signaling in triple-negative breast cancer to promote brain metastases," was published in the journal Oncogene. TNBC is more likely than other types of breast cancer to spread to other parts of the body, that is, to metastasize. It is particularly likely to invade the brain in younger women. But scientists aren't sure why yet. Now, work led by postdoctoral researcher María Contreras-Zárate, PhD, and investigator Diana Cittelly, PhD, at the University of Colorado Cancer Center suggests that a mechanism that was previously viewed as unlikely might actually be the key. Because triple-negative breast cancers lack the receptors for estrogen (as well as progesterone receptors and HER2), they are not expected to be affected by this hormone. However, the researchers proved that, although cancer cells are not directly responsive to estrogen, the hormone can stimulate important brain cells called astrocytes to release factors (chemokines, growth factors, etc.) that promote brain metastases. When mouse models of TNBC
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