Bazedoxifene appears to stop growth of breast cancer cells, including those in treatment-resistant tumors

FDA Highlights by Bruce Sylvester – Bazedoxifene, approved in Europe to treat osteoporosis, appears to stop the growth of breast cancer cells, even in therapy-resistant tumors, researchers from the Duke Cancer Institute, Duke University School of Medicine in Durham, North Carolina, report.

The findings were presented on June 15, 2013, at the annual meeting of The Endocrine Society

“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 lead investigator Donald McDonnell, PhD, chair of Duke’s Department of Pharmacology and Cancer Biology.

Reporting on animal and cell culture studies, the researchers said that bazedoxifene inhibited growth both in estrogen-dependent breast cancer cells and in cells that had developed resistance to the anti-estrogen tamoxifen and/or to the aromatase inhibitors. In current practice, if breast cancer cells become resistant to such therapies, patients usually get toxic chemotherapy and have significant side effects.

Bazedoxifene is an orally delivered drug from the class of drugs known as specific estrogen receptor modulators (SERMs). These drugs act like estrogen in some tissues and block estrogen action in other tissues. Unlike tamoxifen, bazedoxifene can target the estrogen receptor for destruction.

“Because the drug is removing the estrogen receptor as a target by degradation, it is less likely the cancer cell can develop a resistance mechanism because you are removing the target,” said investigator Suzanne Wardell, PhD, a research scientist at Duke.

Wardell explained that many researchers had come to assume that when breast cancer cells developed resistance to tamoxifen, they would remain resistant to any drug targeting the estrogen receptor, “We discovered that the estrogen receptor is still a good target, even after it resistance to tamoxifen has developed,” she said.

Testing involved all breast cancer cell types, including tamoxifen-sensitive cells resistant to lapatinib, which is used to treat patients with advanced breast cancer in patients whose tumors carry the mutant HER2 gene.  Bazedoxifene powerfully inhibited cell growth in this cell type.

In clinical trials, the most often reported side effect of the drug was hot flashes.

Wardell added that, since bazedoxifene has undergone safety and efficacy studies as a treatment for osteoporosis, it may be an alternative soon for patients with advanced breast cancer whose tumors have become resistant to other treatments.

The study was funded by a research grant from Pfizer Pharmaceuticals.