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Annals of Oncology Advance Access published online on May 29, 2008
Annals of Oncology, doi:10.1093/annonc/mdn352
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Imatinib mesylate (Gleevec®) in advanced breast cancer-expressing C-Kit or PDGFR-β: clinical activity and biological correlations

M. Cristofanilli1,*, P. Morandi2, S. Krishnamurthy3, J. M. Reuben4, B.-N. Lee4, D. Francis1, D. J. Booser1, M. C. Green1, B. K. Arun1, L. Pusztai1, A. Lopez5, R. Islam1, V. Valero1 and G. N. Hortobagyi1

1 Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
2 Department of Medical Oncology, San Bortolo Hospital, Vicenza, Italy
3 Department of Pathology
4 Department of Hematopathology
5 Department of Quantitative Sciences, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

* Correspondence to: Dr M. Cristofanilli, Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Box 1354, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Tel: +1-713-792-2817; Fax: +1-713-794-4385; E-mail: mcristof{at}mdanderson.org

Background: Novel molecular therapies for metastatic breast cancer (MBC) are necessary to improve the dismal prognosis of this condition. Imatinib mesylate (Gleevec®) inhibits several protein tyrosine kinases, including platelet-derived growth factor receptor (PDGFR) and c-kit, which are preferentially expressed in tumor cells. We tested the activity of imatinib mesylate in MBC with overexpression of PDGFR or c-kit. Additionally, we sought to determine the biological correlates and immunomodulatory effects.

Patients and methods: Thirteen patients were treated with Imatinib administered orally at 400 mg p.o. b.i.d. (800 mg/day), until disease progression. All patients demonstrated PDGFR-β overexpression and none showed c-kit expression.

Results: No objective responses were observed among the 13 patients treated in an intention-to-treat analysis. All patients experienced disease progression, with a median time to progression of 1.2 months. Twelve patients have died, and the median overall survival was 7.7 months. No patient had a serious adverse event. Imatinib therapy had no effect on the plasma levels of the angiogenesis-related cytokines, vascular endothelial growth factor, PDGF, b-fibroblast growth factor, and E-selectin. Immune studies showed imatinib inhibits interferon-{gamma} production by TCR-activated CD4+ T cells.

Conclusion: Imatinib as a single agent has no clinical activity in PDGFR-overexpressing MBC and has potential immunosuppressive effects.

c-kit expression, imatinib, immune-suppression, metastatic breast cancer

Received for publication February 5, 2008. Revision received April 16, 2008. Accepted for publication April 18, 2008.


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