Brain-targeted estrogen reduces breast cancer treatment side effects

Most breast cancers are worsened by estrogens. To combat the recurrence of these cancers, clinicians treat patients with inhibitors for estrogen production, like letrozole. But many patients do not adhere to this treatment due to negative side effects. Preclinical work in rodents suggests that a drug called 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), which delivers estrogen only to the brain, may be an effective, safe way to reduce these side effects. New in JNeurosci, researchers led by Agnès Lacreuse, from the University of Massachusetts Amherst, explored how DHED works in a more advanced animal model than rodents: aged marmosets. 

Following treatments with letrozole, the research team discovered that treating marmosets with DHED increased estrogen specifically in the brain and improved both memory and sleep. DHED also reversed neural changes from letrozole. DHED had different effects on body temperature regulation in males and females, pointing to the need for more research in this area. 

Says Lacreuse, "Our work suggests that DHED is a promising new hormonal therapy for women with breast cancer and perhaps all menopausal women." The researchers plan to explore the mechanisms DHED acts through in the brain and to assess whether different drug doses improve temperature regulation issues from treatment.