Osteoporosis Drug Stops Growth of Breast Cancer Cells in Tamoxifen-resistant Tumors
A drug approved in Europe to treat osteoporosis has now been shown to stop the growth of breast cancer cells, even in cancers that have become resistant to current targeted therapies, according to a study presented at the Endocrine Society’s 95th Annual Meeting in San Francisco.
The findings indicate that the drug bazedoxifene not only prevents estrogen from fueling breast cancer cell growth, but also flags the estrogen receptor for destruction.
“We found bazedoxifene binds to the estrogen receptor and interferes with its activity, but the surprising thing we then found was that it also degrades the receptor; it gets rid of it,” said senior author Donald McDonnell, PhD, Chair of the Department of Pharmacology and Cancer Biology at the Duke Cancer Institute.
In animal and cell culture studies, the drug inhibited growth both in estrogen-dependent breast cancer cells and in cells that had developed resistance to tamoxifen and/or to aromatase inhibitors, two of the most widely used types of drugs to prevent and treat estrogen-dependent breast cancer. Currently, if breast cancer cells develop resistance to these therapies, patients are usually treated with chemotherapy agents that have significant side effects.
Agent Sidesteps Tamoxifen Resistance
Bazedoxifene is a selective estrogen receptor modulator, like tamoxifen. But unlike tamoxifen, bazedoxifene has some of the properties of a newer group of drugs, known as selective estrogen receptor degraders, which can target the estrogen receptor for destruction.
“Because the drug is removing the estrogen receptor as a target by degradation, it is less likely that the cancer cell can develop a resistance mechanism because you are removing the target,” said lead author Suzanne Wardell, PhD, a research scientist working in Dr. McDonnell’s lab.
Many investigators had assumed that once breast cancer cells developed resistance to tamoxifen, they would be resistant to all drugs that target the estrogen receptor, Dr. McDonnell explained.
“We discovered that the estrogen receptor is still a good target, even after its resistance to tamoxifen has developed,” he said.
Potential Therapeutic Option
The investigators tested a variety of breast cancer cell types, including tamoxifen-sensitive cells that are resistant to lapatinib (Tykerb), another targeted therapy that is used to treat patients with advanced breast cancer whose tumors contain the mutant HER2 gene. These cells had previously been shown to reactivate estrogen signaling in order to acquire drug resistance. In this cell type, bazedoxifene also potently inhibited cell growth.
Paradoxically, in bone tissue, bazedoxifene mimics the action of estrogen, helping protect it from destruction. Because bazedoxifene has already undergone safety and efficacy studies as a treatment for osteoporosis, it may be a viable near-term option for patients with advanced breast cancer whose tumors have become resistant to other treatment options, Dr. Wardell reported. In clinical trials, the most often reported side effect was hot flashes in the bazedoxifene treatment groups.
The study was funded by a research grant from Pfizer Pharmaceuticals, maker of bazedoxifene.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
