Copper depletion therapy keeps high-risk triple-negative breast cancer at bay

An anti-copper drug compound that disables the ability of bone marrow cells from setting up a "home" in organs to receive and nurture migrating cancer tumor cells has shown surprising benefit in one of the most difficult-to-treat forms of cancer - high-risk triple-negative breast cancer.

The median survival for metastatic triple-negative breast cancer patients is historically nine months. However, results of a new phase II clinical trial conducted by researchers at Weill Cornell Medical College and reported in the Annals of Oncology shows if patients at high-risk of relapse with no current visible breast cancer are copper depleted, it results in a prolonged period of time with no cancer recurrence. In fact, only two of 11 study participants with a history of advanced triple-negative breast cancer relapsed within 10 months after using the anti-copper drug, tetrathiomolybdate (TM).

"These study findings are very promising and potentially a very exciting advance in our efforts to help women who are at the highest risk of recurrence," says the study's senior investigator, Dr. Linda Vahdat, director of the Breast Cancer Research Program, chief of the Solid Tumor Service and professor of medicine at Weill Cornell Medical College.

Dr. Vahdat says four of the study participants with a history of metastatic triple-negative breast cancer have had long-term benefit remaining disease free for between three and five and a half years.

"The anti-copper compound appears to be keeping tumors that want to spread in a dormant state," reports Dr. Vahdat, who is also medical oncologist at the Iris Cantor Women's Health Center at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. "We believe one of the important ways it works is by affecting the tumor microenvironment, specifically the bone marrow-derived cells that are critical for metastasis progression."

In addition, study participants with other forms of high-risk for relapse breast cancers - either stage 3 or stage 4 - without evidence of disease after treatment have also fared well. The progression-free survival rate among these 29 patients in the study has been 85 percent, to date.

"As good as these interim findings look to us, we cannot talk about significant benefit until we compare TM treatment to other therapies," she says. Dr. Vahdat expects to launch a phase III randomized clinical trial in the near future.

This research is a report of the first 40 patients. The clinical trial, which began in 2007, has been expanded many times and now includes 60 patients, more than half of who have triple-negative breast cancer.

Deplete Copper to Prevent Cancer Spread
New discoveries in the science of metastasis and examination of the body's utilization of copper to promote cancer spread led to this clinical trial.

Investigators at Weill Cornell, including some of this study's co-authors, have contributed to the recent understanding of the role bone marrow cells play in promoting metastasis. They previously found that a collection of bone marrow-derived cells, which include VEGFR1+ hematopoietic progenitor cells (HPCs), prepare a site in distant organs to accept cancer cells. HPCs also recruit endothelial progenitor cells (EPCs), among others, to activate an "angiogenic switch" that establish blood vessels at the site to feed newly migrated cancer cells.