The existing drug estradiol can inhibit tumor growth in a subtype of triple-negative breast cancer. The researchers may soon test the repurposed drug in a phase II clinical trial.
New findings may improve patient outcomes, as an existing drug inhibits the growth of an aggressive form of breast cancer.
Triple-negative breast cancer is an aggressive form of breast cancer wherein tumors lack expression of three proteins.
The three are estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2).
Triple-negative breast cancer is able to grow and spread more quickly than other forms of breast cancer.
Also, because its cancer cells lack hormone receptors, specialists cannot treat them with hormone therapy. The only treatment for these types of cancer is chemotherapy.
New research, however, has revealed that an existing drug could be repurposed to treat some of the people with this form of breast cancer.
Researchers led by John Hawse, Ph.D., a molecular biologist at the Mayo Clinic in Rochester, MN, tested the effects of estradiol on a subtype of triple-negative breast cancer tumors.
The findings were published in the journal Proceedings of the National Academy of Sciences.
Estradiol and the estrogen receptor beta
“Triple-negative breast cancer is a form of breast cancer that lacks expression of estrogen receptor alpha, progesterone receptor, and [HER2],” explains Hawse, who adds that the condition “exhibits high rates of disease recurrence.”
However, previous research by Hawse and team found that another form of estrogen receptor — called estrogen beta — is present in 25 percent of triple-negative tumors, as well as in over 30 percent of estrogen receptor-positive breast cancer tumors.
That research also showed that the estrogen receptor beta is a tumor suppressor, which correlates with better patient outcomes.
In their new study, Hawse and his colleagues studied the effect of estradiol on the growth of triple-negative tumors that express estrogen receptor beta. The study included both in vitro and in vivo experiments.
“Remarkably,” claims Hawse, “we discovered that estradiol, which normally stimulates [the] growth of cancer cells in tumors that express estrogen receptor alpha, has the opposite effect in triple-negative breast cancer.”
“However, estradiol was only able to inhibit the growth of triple-negative breast cancer when estrogen receptor beta was present,” he adds.
Additionally, the new research illuminates the molecular mechanism through which estradiol fights cancer. When estradiol binds with the estrogen receptor beta, explain the scientists, it induces the secretion of a family of proteins called “cystatins.”
Cystatins inhibit tumor growth and stop cancer cells spreading. “These findings,” say the authors, “suggest that [estrogen receptor beta]-targeted therapies represent a treatment option for the subset of women with [estrogen receptor beta]-expressing [triple-negative breast cancer].”
In the near future, the researchers plan to start a phase II clinical trial that will test how effective estradiol is in the treatment of this type of cancer.
“Estradiol,” says study co-author Dr. Matthew Goetz, a medical oncologist, “is [Food and Drug Administration]-approved as a treatment for women with breast cancer.”
“[H]owever,” he continues, “its use is typically limited to women with estrogen receptor alpha-positive breast cancer that has become resistant to standard therapies.”
“We are excited to study whether estradiol can be repurposed as a new treatment for triple-negative breast cancer that expresses estrogen receptor beta.”
Dr. Matthew Goetz