ABSTRACT
Aromatase inhibitors are the drug of choice for the treatment of estrogen receptor- or progesterone receptor-positive breast cancer in postmenopausal women. Aromatase is an enzyme that catalyzes the final and rate-limiting step in the biosynthesis of estrogen. Inhibitors of this enzyme are an effective therapy for breast cancer. The benefits of these agents have been clearly shown through various clinical trials, yet adherence may be challenging for some patients due to issues of drug interactions, proper first dose education, and adverse effects. Education to prevent and treat adverse effects is of the utmost importance to promote adherence.
ABSTRACT
Tamoxifen is a lifesaving treatment for millions of breast cancer patients worldwide. Yet taking tamoxifen may be challenging for some patients due to issues of compliance, drug interactions, and surgical considerations. Educating patients with a one-page teaching sheet, "Precautions for Patients Taking Tamoxifen," may improve tamoxifen's effectiveness and prevent complications. Advanced practitioners are in a position to prescribe tamoxifen, review medication interactions, educate patients, impact patients' quality of life, improve patients' sense of control, and increase patients' partnerships with their oncology providers.
ABSTRACT
PURPOSE: Bone marrow-derived progenitor cells, including VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways, model the tumor microenvironment. We hypothesized that copper depletion using tetrathiomolybdate would reduce EPCs in high risk for patients with breast cancer who have relapsed. We investigated the effect of tetrathiomolybdate on the tumor microenvironment in preclinical models. EXPERIMENTAL DESIGN: Patients with stage II triple-negative breast cancer (TNBC), stage III and stage IV without any evidence of disease (NED), received oral tetrathiomolybdate to maintain ceruloplasmin (Cp) between 8 and 17 mg/dL for 2 years or until relapse. Endpoints were effect on EPCs and other biomarkers, safety, event-free (EFS), and overall survival (OS). For laboratory studies, MDA-LM2-luciferase cells were implanted into CB17-SCID mice and treated with tetrathiomolybdate or water. Tumor progression was quantified by bioluminescence imaging (BLI), copper depletion status by Cp oxidase levels, lysyl oxidase (LOX) activity by ELISA, and collagen deposition. RESULTS: Seventy-five patients enrolled; 51 patients completed 2 years (1,396 cycles). Most common grade 3/4 toxicity was neutropenia (3.7%). Lower Cp levels correlated with reduced EPCs (P = 0.002) and LOXL-2 (P < 0.001). Two-year EFS for patients with stage II-III and stage IV NED was 91% and 67%, respectively. For patients with TNBC, EFS was 90% (adjuvant patients) and 69% (stage IV NED patients) at a median follow-up of 6.3 years, respectively. In preclinical models, tetrathiomolybdate decreased metastases to lungs (P = 0.04), LOX activity (P = 0.03), and collagen crosslinking (P = 0.012). CONCLUSIONS: Tetrathiomolybdate is safe, well tolerated, and affects copper-dependent components of the tumor microenvironment. Biomarker-driven clinical trials in high risk for patients with recurrent breast cancer are warranted. Clin Cancer Res; 23(3); 666-76. ©2016 AACR.
