An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients.
Ann Oncol
; 22(7): 1561-1570, 2011 Jul.
Article
em En
| MEDLINE
| ID: mdl-21135055
ABSTRACT
BACKGROUND:
Breast cancer cells deficient for BRCA1 are hypersensitive to agents inducing DNA double-strand breaks (DSB), such as bifunctional alkylators and platinum agents. Earlier, we had developed a comparative genomic hybridisation (CGH) classifier based on BRCA1-mutated breast cancers. We hypothesised that this BRCA1-like(CGH) classifier could also detect loss of function of BRCA1 due to other causes besides mutations and, consequently, might predict sensitivity to DSB-inducing agents. PATIENTS ANDMETHODS:
We evaluated this classifier in stage III breast cancer patients, who had been randomly assigned between adjuvant high-dose platinum-based (HD-PB) chemotherapy, a DSB-inducing regimen, and conventional anthracycline-based chemotherapy. Additionally, we assessed BRCA1 loss through mutation or promoter methylation and immunohistochemical basal-like status in the triple-negative subgroup (TN subgroup).RESULTS:
We observed greater benefit from HD-PB chemotherapy versus conventional chemotherapy among patients with BRCA1-like(CGH) tumours [41/230 = 18%, multivariate hazard ratio (HR) = 0.12, 95% confidence interval (CI) 0.04-0.43] compared with patients with non-BRCA1-like(CGH) tumours (189/230 = 82%, HR = 0.78, 95% CI 0.50-1.20), with a significant difference (test for interaction P = 0.006). Similar results were obtained for overall survival (P interaction = 0.04) and when analyses were restricted to the TN subgroup. Sixty-three percent (20/32) of assessable BRCA1-like(CGH) tumours harboured either a BRCA1 mutation (n = 8) or BRCA1 methylation (n = 12).CONCLUSION:
BRCA1 loss as assessed by CGH analysis can identify patients with substantially improved outcome after adjuvant DSB-inducing chemotherapy when compared with standard anthracycline-based chemotherapy in our series.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Carcinoma Basocelular
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Protocolos de Quimioterapia Combinada Antineoplásica
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Receptor ErbB-2
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Proteína BRCA1
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Hibridização Genômica Comparativa
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Mutação
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
Idioma:
En
Revista:
Ann Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2011
Tipo de documento:
Article