Dr Vahdat on the Role of Copper Depletion in Reducing Metastatic Disease Risk in TNBC

Linda Vahdat, MD, MBA, professor of medicine, Geisel School of Medicine at Dartmouth, section chief, Medical Oncology, interim section chief, Hematology, Dartmouth Cancer Center, discusses the role of copper depletion with the copper chelating agent tetrathiomolybdate in potentially decreasing the risk of developing metastatic disease in patients with triple-negative breast cancer (TNBC).

A phase 2 trial (NCT00195091) evaluated tetrathiomolybdate in patients with breast cancer at high risk of recurrence, and findings published in Nature Communications found that that when copper was depleted, patients’ levels of bone marrow–derived progenitor cells were reduced, potentially reducing their chance of relapse.

In a presentation given at the 23rd Annual International Congress on the Future of Breast Cancer® East, Vahdat spoke about findings from the trial that demonstrated that patients with no evidence of disease (NED) stage IV TNBC who underwent copper depletion therapy exhibited an event-free survival (EFS) rate of 59.3% at a median follow-up 9.4 years. In the adjuvant setting, the EFS rate was approximately 88%, Vahdat notes.

These results suggest a significant role of copper in the progression of metastases in patients with TNBC, prompting further exploration into the use of copper depletion as a therapeutic approach.

Vahdat explains that the study also incorporated extensive scientific analysis, which revealed that copper depletion with tetrathiomolybdate effectively reduced levels of bone marrow–derived progenitor cells, which have been linked to relapse in patients with TNBC. Additionally, lower levels of lysyl oxidase 2 were observed in patients who remained with NED, indicating a potential biomarker for stable disease.

Additionally, the study found that copper depletion normalized the collagen microenvironment, which may hinder tumor cell dissemination, Vahdat explains.

Preclinical findings supported this phenomenon, showing that although copper depletion does not impact primary tumor size, it significantly reduced metastasis risk by decreasing the number of disseminated tumor cells and preventing their subsequent detachment and invasion, she continues.

Copper depletion with tetrathiomolybdate is a promising strategy to mitigate metastasis risk in TNBC, Vahdat concludes, noting that further research is needed to fully understand the mechanisms of copper depletion and optimize its clinical application in this high-risk patient population.