The Copper
Paradox

“I’ve always wondered why patients can be fine after having breast cancer, and then, 20 years later, suddenly their tumor comes back,” says Vahdat, a practicing oncologist. “What makes cells come out of dormancy? Obviously, they’re hiding somewhere, waiting for a signal.”

The question of what that signal might be has driven Vahdat’s research for over two decades, leading her to explore the role of copper in cancer metastasis, particularly in the rare but aggressive triple-negative breast cancer (TNBC).

The Copper Connection

TNBC does not grow in the same way as most common types of breast cancer, making it difficult to treat successfully with existing medications. It represents 17-20% of all breast cancer cases, but accounts for over 50% of breast cancer metastases and 30% of all breast cancer deaths. The disease also more often affects young women, women with a high-risk BRCA1 mutation, and African Americans.

Vahdat has dedicated her career to TNBC. “I’ve always been focused on the highest risk patients,” says Vahdat, who is also the section chief of Medical Oncology at the Cancer Center. “My life’s mission is to figure out how breast cancer spreads and to stop it.”

Copper is crucial for many bodily functions, including forming blood cells and healthy nerve function. However, Vahdat’s research has revealed that “if you have too much copper available, it can get shifted to other functions, including tumor metastasis,” she explains.

Vahdat’s current research on copper depletion in TNBC has its roots in work by researchers at the University of Michigan in the 1990s. These original studies focused on metastatic breast cancer and were considered unsuccessful by conventional standards, as they did not achieve tumor shrinkage. Still, Vahdat found the results intriguing: while tumors did not shrink, they also did not spread. “I thought that was an interesting juxtaposition,” she says.

A New Approach to Prevention

Inspired by these findings, Vahdat immersed herself in scientific literature on copper depletion in cancer. A pivotal moment came in 2003 when she encountered a study involving mice genetically programmed to develop lung metastases. This study demonstrated that mice treated with a copper-depleting compound, tetrathiomolybdate (TM), did not develop lung metastases, whereas untreated mice did.

TM works by reducing copper levels in the body, which is crucial for cancer growth and metastasis. “When TM treatment was withdrawn from the mice that had received it, they later developed lung metastases,” Vahdat says. “This suggested that copper plays a vital role in creating the environment necessary for cancer to spread. By depleting copper with TM, we were essentially removing the infrastructure that cancer needs to metastasize.”