Abstract P4-09-01: Poly (ADP-ribose) Polymerase-1 mRNA Expression in Human Breast Cancer: Correlations with Subtypes and Prognostic Impact

Abstract

Abstract Introduction: Although poly(ADP-ribose) polymerase-1 (PARP1) inhibition is a recent promising therapy in breast cancer, PARP1 expression in this disease is not known. Methods. Using DNA microarray and array-based comparative genomic hybridization (arrayCGH), we examined PARP1 mRNA expression and copy number alterations in 326 invasive breast cancer samples and normal breast samples. A meta-analysis was performed on a large public retrospective gene expression dataset (n= 2,485) to analyze correlation between PARP1 mRNA expression and molecular subtypes and clinico-pathological parameters. Results. PARP1 was overexpressed in 58% of cancers, and its expression was heterogeneous between tumors. ArrayCGH data revealed an association between mRNA overexpression and gain/amplification at the PARP1 locus (p<1.0E-8). Meta-analysis showed that PARP1 expression was higher in basal breast cancers (p<1.0E-72), but overexpression was also found in other subtypes. PARP1 expression correlated with high grade, medullary histological type, tumor size and worse metastasis-free survival (HR=1.12 [1.04-1.22]; p=0.004). In multivariate analysis, PARP1 expression had an independent prognostic value, which was restricted to patients untreated with any adjuvant chemotherapy. Univariate and multivariate analyses in MFS in patients untreated with systemic adjuvant chemotherapy Conclusion. These data demonstrate overexpression of PARP1 in a large number of breast cancers and its association with reduced metastasis-free survival. These results further support the development of PARP inhibitors in basal subtype but also potentially in other breast cancer subtypes. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-01.