Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse.
Ann Oncol
; 24(6): 1491-8, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-23406736
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 ANDMETHODS:
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
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Neoplasias da Mama
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Cobre
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Células Endoteliais
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Molibdênio
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Recidiva Local de Neoplasia
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article