Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse

Research output: Contribution to journalArticle

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, Vivek Mittal, S. Rafii, L. T. Vahdat

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.

Original languageEnglish
Pages (from-to)1491-1498
Number of pages8
JournalAnnals of Oncology
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2013

PMID: 23406736

PMCID: PMC3707432

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Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse. / Jain, S.; Cohen, J.; Ward, M. M.; Kornhauser, N.; Chuang, E.; Cigler, T.; Moore, A.; Donovan, D.; Lam, C.; Cobham, M. V.; Schneider, S.; Hurtado Rúa, S. M.; Benkert, S.; Mathijsen Greenwood, C.; Zelkowitz, R.; Warren, J. D.; Lane, M. E.; Mittal, Vivek; Rafii, S.; Vahdat, L. T.

In: Annals of Oncology, Vol. 24, No. 6, 01.06.2013, p. 1491-1498.

Research output: Contribution to journalArticle

Harvard

Jain, S, Cohen, J, Ward, MM, Kornhauser, N, Chuang, E, Cigler, T, Moore, A, Donovan, D, Lam, C, Cobham, MV, Schneider, S, Hurtado Rúa, SM, Benkert, S, Mathijsen Greenwood, C, Zelkowitz, R, Warren, JD, Lane, ME, Mittal, V, Rafii, S & Vahdat, LT 2013, 'Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse' Annals of Oncology, vol. 24, no. 6, pp. 1491-1498. https://doi.org/10.1093/annonc/mds654

APA

Jain, S., Cohen, J., Ward, M. M., Kornhauser, N., Chuang, E., Cigler, T., ... Vahdat, L. T. (2013). Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse. Annals of Oncology, 24(6), 1491-1498. https://doi.org/10.1093/annonc/mds654

Vancouver

Jain S, Cohen J, Ward MM, Kornhauser N, Chuang E, Cigler T et al. Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse. Annals of Oncology. 2013 Jun 1;24(6):1491-1498. https://doi.org/10.1093/annonc/mds654

Author

Jain, S. ; Cohen, J. ; Ward, M. M. ; Kornhauser, N. ; Chuang, E. ; Cigler, T. ; Moore, A. ; Donovan, D. ; Lam, C. ; Cobham, M. V. ; Schneider, S. ; Hurtado Rúa, S. M. ; Benkert, S. ; Mathijsen Greenwood, C. ; Zelkowitz, R. ; Warren, J. D. ; Lane, M. E. ; Mittal, Vivek ; Rafii, S. ; Vahdat, L. T. / Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse. In: Annals of Oncology. 2013 ; Vol. 24, No. 6. pp. 1491-1498.

BibTeX

@article{c9df1299d3b946449476184136424535,
title = "Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse",
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.",
keywords = "Breast cancer, Endothelial progenitor cells, Tetrathiomolybdate",
author = "S. Jain and J. Cohen and Ward, {M. M.} and N. Kornhauser and E. Chuang and T. Cigler and A. Moore and D. Donovan and C. Lam and Cobham, {M. V.} and S. Schneider and {Hurtado R{\'u}a}, {S. M.} and S. Benkert and {Mathijsen Greenwood}, C. and R. Zelkowitz and Warren, {J. D.} and Lane, {M. E.} and Vivek Mittal and S. Rafii and Vahdat, {L. T.}",
year = "2013",
month = "6",
day = "1",
doi = "10.1093/annonc/mds654",
language = "English",
volume = "24",
pages = "1491--1498",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "6",

}

RIS

TY - JOUR

T1 - Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse

AU - Jain, S.

AU - Cohen, J.

AU - Ward, M. M.

AU - Kornhauser, N.

AU - Chuang, E.

AU - Cigler, T.

AU - Moore, A.

AU - Donovan, D.

AU - Lam, C.

AU - Cobham, M. V.

AU - Schneider, S.

AU - Hurtado Rúa, S. M.

AU - Benkert, S.

AU - Mathijsen Greenwood, C.

AU - Zelkowitz, R.

AU - Warren, J. D.

AU - Lane, M. E.

AU - Mittal, Vivek

AU - Rafii, S.

AU - Vahdat, L. T.

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Endothelial progenitor cells

KW - Tetrathiomolybdate

UR - http://www.scopus.com/inward/record.url?scp=84878467452&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878467452&partnerID=8YFLogxK

U2 - 10.1093/annonc/mds654

DO - 10.1093/annonc/mds654

M3 - Article

VL - 24

SP - 1491

EP - 1498

JO - Annals of Oncology

T2 - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 6

ER -

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