Abstract | BACKGROUND: Bone marrow-derived endothelial progenitor cells (EPCs) are critical for metastatic progression. This study explores the effect of tetrathiomolybdate (TM), an anti-angiogenic copper chelator, on EPCs in patients at high risk for breast cancer recurrence. PATIENTS AND METHODS: This phase 2 study enrolled breast cancer patients with stage 3 and stage 4 without evidence of disease (NED), and stage 2 if triple-negative. TM 100 mg orally was administered to maintain ceruloplasmin <17 mg/dl for 2 years or until relapse. The primary end point was change in EPCs. RESULTS: Forty patients (28 stage 2/3, 12 stage 4 NED) were enrolled. Seventy-five percent patients achieved the copper depletion target by 1 month. Ninety-one percent of triple-negative patients copper-depleted compared with 41% luminal subtypes. In copper-depleted patients only, there was a significant reduction in EPCs/ml by 27 (P = 0.04). Six patients relapsed while on study, of which only one patient had EPCs maintained below baseline. The 10-month relapse-free survival was 85.0% (95% CI 74.6%-96.8%). Only grade 3/4 toxicity was hematologic: neutropenia (3.1% of cycles), febrile neutropenia (0.2%), and anemia (0.2%). CONCLUSIONS: TM is safe and appears to maintain EPCs below baseline in copper-depleted patients. TM may promote tumor dormancy and ultimately prevent relapse.
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Authors | S Jain, J Cohen, M M Ward, N Kornhauser, E Chuang, T Cigler, A Moore, D Donovan, C Lam, M V Cobham, S Schneider, S M Hurtado Rúa, S Benkert, C Mathijsen Greenwood, R Zelkowitz, J D Warren, M E Lane, V Mittal, S Rafii, L T Vahdat |
Journal | Annals of oncology : official journal of the European Society for Medical Oncology
(Ann Oncol)
Vol. 24
Issue 6
Pg. 1491-8
(Jun 2013)
ISSN: 1569-8041 [Electronic] England |
PMID | 23406736
(Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chelating Agents
- Copper
- Molybdenum
- tetrathiomolybdate
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Topics |
- Adult
- Aged
- Breast Neoplasms
(blood, diagnosis, drug therapy)
- Chelating Agents
(therapeutic use)
- Copper
(blood)
- Endothelial Cells
(drug effects, metabolism)
- Female
- Humans
- Middle Aged
- Molybdenum
(pharmacology, therapeutic use)
- Neoplasm Recurrence, Local
(blood, prevention & control)
- Risk Factors
- Stem Cells
(drug effects, metabolism)
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