In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 21 ( 2009-07-20), p. 3430-3436
Abstract:
We have demonstrated that patients with HER2-amplified tumors derive more benefit from higher doses of doxorubicin-containing chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil [CAF]). Because topoisomerase IIα (Topo-IIα) is a target for doxorubicin and is coamplified in 20% to 50% of HER2-amplified tumors, we postulated that Topo-IIα copy number might account for the benefit from CAF dose escalation in HER2-positive tumors. To address this hypothesis, we examined Topo-IIα and HER2 copy number, CAF dose, and clinical outcomes in Cancer and Leukemia Group B (CALGB) 8541. Patients and Methods Topo-IIα and HER2 copy number were measured by fluorescent in situ hybridization (FISH) using a triple-probe system, which includes Topo-IIα, HER2, and chromosome 17 (CEP17). Topo-IIα and/or HER2 were classified as amplified (≥ two copies/CEP17, deleted (≤ 0.67 copies/CEP17) and normal copy number ( 〉 .67 to 〈 2.0 copies/CEP17). Results Topo-IIα/HER2/CEP17 measurement was successful in 624 of 687 cases. HER2 was amplified in 117 cases (19%). Topo-IIα was amplified in 41 cases (7%) and deleted in 69 cases (11%). Topo-IIα amplification was highly correlated with HER2 amplification (39 of 41; P 〈 .0001), HER2 by immunohistochemistry, and by dual-probe FISH. Topo-IIα was deleted in both the HER2-amplified (30 of 69; 43%), normal (22 of 69; 32%) and HER2-deleted tumors (17 of 69; 25%). Although Topo-IIα–amplified tumors were nearly always HER2 amplified, these tumors did not receive benefit from increasing the dose of CAF (P = .15). Conclusion The correlative companion study CALGB 8541-150013 does not support the hypothesis that Topo-IIα amplification is the mechanism behind benefit from increased dose of anthracyclines in HER2-positive breast cancer.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2008.18.4085
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2009
detail.hit.zdb_id:
2005181-5
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