The Copper Paradox: Linda Vahdat’s Mission to Prevent Cancer Metastasis
Copper, to the human body, is an essential nutrient for life. But when it comes to cancer, copper’s role in our health may be more complicated, according to research by Linda Vahdat, MD, MBA, deputy director of Dartmouth Cancer Center. In fact, Vahdat’s discovery of copper’s detrimental effects—specifically in cancer patients—could be key to groundbreaking treatments for one of the most aggressive forms of breast cancer.
“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.”
These insights led Vahdat to initiate her own phase II clinical trial in 2007 while at Weill Cornell Medicine. That trial focused on high-risk breast cancer patients, including those with TNBC, and aimed to explore whether TM could prevent cancer recurrence in humans as effectively as it had in mice. This important study continued enrolling patients until 2014, involving 75 women with a median follow-up of 10.4 years. The copper depletion approach was found to be safe, well-tolerated, and promising in reducing relapse rates.
Now, Vahdat is leading a new phase II trial at Dartmouth Cancer Center. “We are so excited about this. We can't wait to get started,” Vahdat says.
Turning Trials into Cures
Philanthropy has been crucial in advancing this research, especially now that it’s reached the clinical trials stage. The Margaret Claire Pisani Fund, named after one of Vahdat's former patients, has significantly supported Vahdat’s work. “None of this would happen without philanthropy—zero,” Vahdat states.
Vahdat's new phase II clinical trial, which is distinct from the earlier studies, will be conducted across eight different sites, including Dartmouth Cancer Center. The primary purpose is to further validate TM’s safety and efficacy, offering a potentially new strategy for TNBC patients who face limited options.
“My goal is to get the word out that there is a strategy that’s not chemo, not immunotherapy, that can potentially help them,” Vahdat says. “The only way to advance treatment is by proving new treatments work, and the way to prove that they work is by doing clinical trials.”
This trial will span six years, with three years dedicated to patient accrual and three years for follow-up. It represents a culmination of years of work and a chance to offer new hope to those at highest risk of cancer recurrence. Overall, the study aims to enroll 186 patients over five years to determine if adding copper depletion to standard treatments further decreases relapse rates and extends survival.
“It takes a village to do this—patients, families, people from all walks of life are involved,” Vahdat reflects. “We're really looking forward to being able to offer this as an option to patients, and we hope that when we have the results of our trial, it shows that it made a difference.”
To learn more about how to support breast cancer research, please contact Erin Shreve at Erin.Shreve@hitchcock.org or 603-646-5878.
