Severson TM, et al. – This study intended to figure out whether the BRCA1–like signature to an expression–based signature (BRC1Aness) signature was associated significantly with response to PARP inhibitor treatment versus control in the I–SPY 2 randomized neoadjuvant setting. A successful translation of a genomic–based BRC1Aness, was noticed. Moreover, the BRCA1ness signature was capable of predicting the benefit of V–C added to standard chemotherapy compared to standard chemotherapy alone.

Methods

• By using a centroid model with 128 triple-negative breast cancer samples from the EU FP7 RATHER project, a diagnostic gene expression signature (BRCA1ness) was developed.
• Furthermore, this BRCA1ness signature was 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.
• 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, were evaluated.

Results

• A gene expression signature was developed to identify BRCA1-like status.
• Although not in the control arm (p=0.45), in the I-SPY 2 neoadjuvant setting the BRCA1ness signature associated significantly with response to V-C (p=0.03).
• A significant interaction was observed between BRCA1ness and V-C (p=0.023) after correcting for HR.