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Planetary boundary layer

“The cancer cells aren’t responsive to estrogen, but estrogen influences the microenvironment. We found that astrocytes — one of the main components of the microenvironment in the brain — are estrogen-responsive. When they are stimulated with estrogen, they produce chemokines, growth factors, and other things that promote brain metastasis,” says Diana Cittelly, PhD, investigator at CU Cancer Center and assistant professor in the CU School of Medicine Department of Pathology.

Technically, Cittelly and colleagues including postdoctoral researcher, Maria Contreras-Zarate, PhD, found that estrogen induces astrocytes (brain cells) to produce growth factors called brain-derived neurotrophic factor (BDNF) and Epidermal Growth Factor (EGF), and that these factors turns on two genetic migration/invasion switches in cancer cells, namely TRKB and EGFR.

“This may explain why breast cancers diagnosed in younger women are more likely to metastasize to the brain — pre-menopausal women have more estrogen, and it may be influencing the microenvironment of the brain in ways that aid cancer,” Cittelly says.

Traditionally, estrogen-positive cancers have been treated with anti-estrogen receptor therapies including tamoxifen. However, it has always seemed obvious that cancers without estrogen receptors would not respond to anti-estrogen receptor therapy. And, unfortunately, there has been little opportunity to accidentally notice the effects of anti-estrogen therapy on brain metastases resulting from breast cancer.

“Historically, women with brain