PARP-1 expression in breast cancer including BRCA1-associated, triple negative and basal-like tumors: possible implications for PARP-1 inhibitor therapy

• DOI: 10.1007/s10549-011-1441-2
• Publication Date: 2011-03-16T08:15:38Z
• Authors: Pawel Domagala; Tomasz Huzarski; Jan Lubinski; Karol Gugala; Wenancjusz Domagala
• Keywords: Genotype; BRCA1 Protein; Poly (ADP-Ribose) Polymerase-1; Breast Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Polymerase Chain Reaction; 3. Good health; ErbB Receptors; 03 medical and health sciences; 0302 clinical medicine; Receptors, Estrogen; Tissue Array Analysis; Cell Line, Tumor; Biomarkers, Tumor; Humans; Female; Poly(ADP-ribose) Polymerases; Receptors, Progesterone; In Situ Hybridization

Despite ongoing trials of PARP inhibitors in the treatment of breast cancer (BC), the extent of poly(ADP-ribose)polymerase-1 (PARP-1) protein expression in BCs, which may influence treatment results, is not known. The purpose of this report is to assess expression of PARP-1 in BC including BRCA1-associated, triple negative (TN), and basal-like tumors. Immunohistochemistry with a PARP-1 antibody on tissue microarrays from 130 BRCA1-associated and 594 BRCA1-non-related BCs was used. The vast majority of breast carcinomas expressed high level of nuclear PARP-1 protein and a small percentage of tumors exhibited both nuclear and cytoplasmic PARP-1 expression. There was a significant difference between the mean nuclear PARP-1 quickscore in BRCA1-associated versus BRCA1-non-associated carcinomas in all tumors (P < 0.0001), in the basal-like group (P = 0.0086), TN (P = 0.0015), and non-basal-like groups (P = 0.016) but not in the non-TN group. Among BRCA1-associated BCs, low PARP-1 expression was found in 18.5% of all cases, 18.9% of basal-like and 21% of TN cancers. Among BRCA1-non-related tumors, low PARP-1 expression was found in 8.8% of all cases, 3.1% of basal-like, and 2.7% of TN cancers. PARP-1 expression is significantly associated with BRCA1 status in basal-like and TN BCs. The assessment of PARP-1 expression in tumor samples may improve the selection of BC patients for PARP inhibitor therapy.