The BRCA1ness signature is associated significantly with response to PARP inhibitor treatment versus control in the I-SPY 2 randomized neoadjuvant setting

Autor: Tesa M. Severson, Denise M. Wolf, Christina Yau, Justine Peeters, Diederik Wehkam, Philip C. Schouten, Suet-Feung Chin, Ian J. Majewski, Magali Michaut, Astrid Bosma, Bernard Pereira, Tycho Bismeijer, Lodewyk Wessels, Carlos Caldas, René Bernards, Iris M. Simon, Annuska M. Glas, Sabine Linn, Laura van ‘t Veer
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Breast Cancer Research, Vol 19, Iss 1, Pp 1-9 (2017)
Druh dokumentu: article
ISSN: 1465-542X
DOI: 10.1186/s13058-017-0861-2
Popis: Abstract Background Patients with BRCA1-like tumors correlate with improved response to DNA double-strand break-inducing therapy. A gene expression-based classifier was developed to distinguish between BRCA1-like and non-BRCA1-like tumors. We hypothesized that these tumors may also be more sensitive to PARP inhibitors than standard treatments. Methods A diagnostic gene expression signature (BRCA1ness) was developed using a centroid model with 128 triple-negative breast cancer samples from the EU FP7 RATHER project. This BRCA1ness signature was then tested in HER2-negative patients (n = 116) from the I-SPY 2 TRIAL who received an oral PARP inhibitor veliparib in combination with carboplatin (V-C), or standard chemotherapy alone. We assessed the association between BRCA1ness and pathologic complete response in the V-C and control arms alone using Fisher’s exact test, and the relative performance between arms (biomarker × treatment interaction, likelihood ratio p
Databáze: Directory of Open Access Journals
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