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Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 501
© 2005 American Society of Clinical Oncology
HER2 genetic polymorphism and pharmacodynamics of trastuzumab-based treatment in breast cancer patients
G. A. Milano,
W. Lescaut,
J. L. Formento,
R. Largillier,
M. Campone,
E. Chamorey,
M. Francoual and
J. M. Ferrero
Ctr Antoine-Lacassagne, Nice, France; Ctr René Gauducheau, Nantes, France
501
Background: A single SNP at codon 655 (Val655Ile) in the transmembrane domain of HER2 gene was shown to be associated with an increased risk of breast cancer (Xie et al, J Natl Cancer Inst, 2000). A model for the activation of HER2 suggests that this Val/Ile substitution could destabilize the formation of active HER2 dimers (Fleishman et al, PNAS, 2002). These findings led us to explore the possible association between HER2 genotype and the pharmacodynamics of HER2 targeting therapy with Herceptin. Methods: Genomic DNA from 57 consecutive advanced breast cancer patients (mean 57 years, 33–83) receiving a herceptin-based treatment (combined with paclitaxel for the majority) were examined for the Val655Ile polymorphism with a PCR-RFLP based assay. Results: The genotype repartition (%) was 7 for ValVal, 36.9 for Ile/Val and 56.1 for Ile/Ile. There was no significant link between HER2 genotype and objective response rate (66% for Val/Ile + Val/Val and 65% for Ile/Ile), disease-free survival (median, months: 21 for Val/Ile + Val/Val and 18 for Ile/Ile) and overall survival (median, months: not reached for Val/Ile + Val/Val and 48 for Ile/Ile). Of note, there were 5 cases of herceptin-linked cardiotoxicity and all these patients carried the Val allele (p=0.008). Conclusion: These results suggest for the first time a potential clinical value for HER2 genetic polymorphism in the management of herceptin-based treatment.
Abstract presentation from the 2005 ASCO Annual Meeting
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