Altering the tumor microenvironment: A phase II study of copper depletion using tetrathiomolybdate (TM) in patients (pts) with breast cancer (BC) at high risk for recurrence.

11008 Background: Bone marrow derived endothelial progenitor cells (EPCs) and copper-dependent pathways are critical components to remodeling the tumor microenvironment and creating the pre-metastatic niche. Copper depletion (CD) inhibits tumor metastases in preclinical models. We hypothesized that TM-associated CD would reduce EPCs and other copper dependent processes in the pre-metastatic niche in BC pts at high risk for relapse. We investigated the relationship between CD and its effect on EPCs and other components of the tumor microenvironment including lysyl oxidase (LOX). Methods: In this single arm, phase II study, BC pts at high risk for recurrence, defined as node+ triple negative (TN), stage 3 and 4 with no evidence of disease (NED) were enrolled on a trial of CD with TM. We utilized TM to maintain ceruloplasmin (Cp) between 5-17 mg/dl until end of treatment or relapse. The primary endpoint was change in EPCs measured by flow cytometry before and during treatment with TM. Secondary endpoints inc...