Osteoporosis drug stops growth of breast cancer cells, even in 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 Duke Cancer Institute study.

The findings, presented June 15, 2013, at the annual Endocrine Society meeting in San Francisco, indicate that the drug bazedoxifene packs a powerful one-two punch that 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 Duke's Department of Pharmacology and Cancer Biology.

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 the anti-estrogen tamoxifen and/or to the 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 toxic chemotherapy agents that have significant side effects.

Bazedoxifene is a pill that, like tamoxifen, belongs to a class of drugs known as specific estrogen receptor modulators (SERMs). These drugs are distinguished by their ability to behave like estrogen in some tissues, while significantly blocking estrogen action in other tissues. But unlike tamoxifen, bazedoxifene has some of the properties of a newer group of drugs, known as selective estrogen receptor degraders, or SERDs, 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 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 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, McDonnell explained.

"We discovered that the estrogen receptor is still a good target, even after it resistance to tamoxifen has developed," he said.

Breast Cancer Stem Cell Research Breast cancer stem cells were discovered in 2003 by scientists at the U-M Comprehensive Cancer Center In the fight against breast cancer, there is good news and bad news. The good news is that, since 1990, there has been a steady decline in the death rate from breast cancer. Earlier detection and better treatments are bringing hope to people with both early and advanced disease.

The bad news is that more than 40,000 people die from breast cancer every year in the United States alone. It is still the second-leading cause of deaths from cancer in women. The survival rate for those with advanced, metastatic breast cancer has not changed significantly for decades. In spite of more effective therapies, many patients still experience recurrences of breast cancer after treatment.