A new analysis has identified the hormone estrone as a key driver of aggressive breast cancer in post-menopausal women with obesity. The findings suggest that weight-loss drugs could help improve treatment outcomes.
The study focuses on oestrogen receptor-positive (ER+) breast cancer—the most common and deadly form of the disease in women after menopause.
“They are more likely to be diagnosed with this form of the disease, and they are two to three times more likely to die from it,” said Dr. Joyce Slingerland, co-leader of the Cancer Host Interaction Program at Georgetown University’s Lombardi Comprehensive Cancer Center. “This is particularly concerning as obesity is projected to affect nearly half of women in the U.S. by the end of the decade.”
Estrone: The Overlooked Oestrogen
Slingerland’s analysis points to estrone—a hormone produced in fat tissue—as a major factor in breast cancer progression in obese, post-menopausal women. Estrone becomes the dominant oestrogen after menopause, overtaking 17β-oestradiol, which is produced by the ovaries and regulates inflammation before menopause.
Despite chemical similarities, these two oestrogens behave differently. “Simply put, these two oestrogens are not equal,” Slingerland said. Her earlier research showed that 17β-oestradiol reduces inflammation by blocking NFκB proteins, while estrone combines with NFκB to activate genes that trigger widespread inflammation.
How Estrone Fuels Cancer
In women with obesity, estrone levels in fat and breast tissue are two to four times higher than normal. This surge triggers inflammation that can promote precancerous changes and activate cancer-driving genes.
A 2022 study found that estrone-driven inflammation activates genes involved in epithelial-mesenchymal transition, a process linked to cancer metastasis. In experiments on obese mice with ER+ breast cancer, estrone accelerated tumor growth and encouraged rapid cancer spread. Estrone may also suppress immune responses, making it harder for the body to detect and fight cancer.
“These findings should prompt us to rethink cancer treatment strategies for these women,” Slingerland said.
Potential Role of GLP-1 Weight-Loss Drugs
Given the connection between estrone, inflammation, and cancer progression, Slingerland recommends clinical trials of GLP-1 receptor agonists in obese women with ER+ breast cancer. While lifestyle changes like diet and exercise have shown some benefit, their long-term impact remains uncertain.
“The GLP-1 drugs have revolutionized weight loss,” Slingerland said. “Because estrone has strong inflammatory effects in fat, these drugs could potentially slow its cancer-fueling activity.”
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