BRCAness digitalMLPA profiling predicts benefit of intensified platinum-based chemotherapy in triple-negative and luminal-type breast cancer.
Breast Cancer Res
; 22(1): 79, 2020 07 25.
Article
em En
| MEDLINE
| ID: mdl-32711554
ABSTRACT
BACKGROUND:
We previously showed that BRCA-like profiles can be used to preselect individuals with the highest risk of carrying BRCA mutations but could also indicate which patients would benefit from double-strand break inducing chemotherapy. A simple, robust, and reliable assay for clinical use that utilizes limited amounts of formalin-fixed, paraffin-embedded tumor tissue to assess BRCAness status in both ER-positive and ER-negative breast cancer (BC) is currently lacking.METHODS:
A digital multiplex ligation-dependent probe amplification (digitalMLPA) assay was designed to detect copy number alterations required for the classification of BRCA1-like and BRCA2-like BC. The BRCA1-like classifier was trained on 71 tumors, enriched for triple-negative BC; the BRCA2-like classifier was trained on 55 tumors, enriched for luminal-type BC. A shrunken centroid-based classifier was developed and applied on an independent validation cohort. A total of 114 cases of a randomized controlled trial were analyzed, and the association of the classifier result with intensified platinum-based chemotherapy response was assessed.RESULTS:
The digitalMLPA BRCA1-like classifier correctly classified 91% of the BRCA1-like samples and 82% of the BRCA2-like samples. Patients with a BRCA-like tumor derived significant benefit of high-dose chemotherapy (adjusted hazard ratio (HR) 0.12, 95% CI 0.04-0.44) which was not observed in non-BRCA-like patients (HR 0.9, 95% CI 0.37-2.18) (p = 0.01). Analysis stratified for ER status showed borderline significance.CONCLUSIONS:
The digitalMLPA is a reliable method to detect a BRCA1- and BRCA2-like pattern on clinical samples and predicts platinum-based chemotherapy benefit in both triple-negative and luminal-type BC.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Proteína BRCA1
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Proteína BRCA2
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Neoplasias de Mama Triplo Negativas
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Mutação
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prognostic_studies
Limite:
Adult
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Female
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article