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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 ( BRCA1 ness) was developed using a centroid model with 128 triple-negative breast cancer samples from the EU FP7 RATHER project. This  BRCA1 ness 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  BRCA1 ness 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  < 0.05) using a logistic model and adjusting for hormone receptor status (HR).    Results  We developed a gene expression signature to identify  BRCA1 -like status. In the I-SPY 2 neoadjuvant setting the  BRCA1 ness signature associated significantly with response to V-C ( p  = 0.03), but not in the control arm ( p  = 0.45). We identified a significant interaction between  BRCA1 ness and V-C ( p  = 0.023) after correcting for HR.    Conclusions  A genomic-based  BRCA1 -like signature was successfully translated to an expression-based signature ( BRC1A ness). In the I-SPY 2 neoadjuvant setting, we determined that the  BRCA1 ness signature is capable of predicting benefit of V-C added to standard chemotherapy compared to standard chemotherapy alone.    Trial registration  I-SPY 2 TRIAL beginning December 31, 2009: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (I-SPY 2),  NCT01042379 .    Electronic supplementary material  The online version of this article (doi:10.1186/s13058-017-0861-2) contains supplementary material, which is available to authorized users.

breast cancer research

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