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J Clin Oncol. 2009 Aug 20;27(24):3881-6. doi: 10.1200/JCO.2008.20.1566. Epub 2009 Jul 20.

Outcome of patients with early-stage breast cancer treated with doxorubicin-based adjuvant chemotherapy as a function of HER2 and TOP2A status.

Author information

1
Department of Molecular Pathology, Cleveland Clinic, Cleveland, OH 44195, USA. TubbsR@ccf.org

Abstract

PURPOSE:

Amplification and deletion of the TOP2A gene have been reported as positive predictive markers of response to anthracycline-based therapy. We determined the status of the HER2 and TOP2A genes in a large cohort of breast cancer patients treated with adjuvant doxorubicin (A) and cyclophosphamide (C).

PATIENTS AND METHODS:

TOP2A/CEP17 and HER2/CEP17 fluorescent in situ hybridization (FISH) were performed on tissue microarrays (TMAs) constructed from 2,123 of the 3,125 women with moderate-risk primary breast cancer who received equivalent doses of either concurrent adjuvant chemotherapy with A plus C (n = 1,592) or sequential A followed by C (n = 1,533).

RESULTS:

An abnormal TOP2A genotype was identified for 153 (9.4%) of 1,626 patients (4.0% amplified; 5.4% deleted). An abnormal HER2 genotype was identified for 303 (20.4%) of 1,483 patients (18.8% amplified; 1.6% deleted). No significant differences in either overall survival (OS) or disease-free survival (DFS) were identified for TOP2A. In univariate analysis, OS and DFS rates were strongly and adversely associated only with higher levels of HER2 amplification (ratio > or = 4.0). Survival was not associated with low-level HER2 amplification (ratio > or = 2; OS hazard ratio [HR], 1.14; P = .39; DFS HR, 1.07; P = .62), but it was associated for a ratio > or = 4 (OS HR, 1.45; P = .03; DFS HR, 1.38; P = .033), in which analysis was adjusted for menopausal status, hormone receptor status, treatment, number of positive nodes, and tumor size.

CONCLUSION:

In this population of patients with early-stage breast cancer who were treated with adjuvant AC chemotherapy, TOP2A abnormalities were not associated with outcome. HER2 high-level amplification was a prognostic marker in anthracycline-treated patients.

PMID:
19620488
PMCID:
PMC2734394
DOI:
10.1200/JCO.2008.20.1566
[Indexed for MEDLINE]
Free PMC Article

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