PARP-1 Expression and BRCA1 Mutations in Breast Cancer Patients' CTCs.

Abstract

Simple SummaryRecent estimates have shown that approx. 70% of individuals with BRCA1 mutations will develop breast cancer by the age of 70. To make matters worse, breast cancer patients with BRCA1 mutations are more likely to have the more aggressive triple-negative breast cancer. PARPs, belong to a family of nuclear enzymes, which are involved in many cellular processes, including DNA repair. PARP inhibitors have been approved for the treatment of BRCA-mutated breast cancer. The aim of the study was the determination of PARP-1 expression in the context of the presence of BRCA1 mutations in circulating tumor cells of breast cancer patients. PARP-1 (nuclear) expression and BRCA1 mutations were mainly detected in triple negative breast cancer patients, and the latter were correlated with decreased survival. Our data suggest that PARP-1, in conjunction with BRCA1, could potentially be used as (a) biomarker(s) for patients’ stratification.BRCA1 and PARP are involved in DNA damage repair pathways. BRCA1 mutations have been linked to higher likelihood of triple negative breast cancer (TNBC). The aim of the study was to determine PARP-1 expression and BRCA1 mutations in circulating tumor cells (CTCs) of BC patients. Fifty patients were enrolled: 23 luminal and 27 TNBC. PARP expression in CTCs was identified by immunofluorescence. Genotyping was performed by PCR-Sanger sequencing in the same samples. PARP-1 expression was higher in luminal (61%) and early BC (54%), compared to TNBC (41%) and metastatic (33%) patients. In addition, PARP-1 distribution was mostly cytoplasmic in luminal patients (p = 0.024), whereas it was mostly nuclear in TNBC patients. In cytokeratin (CK)-positive patients, those with the CK+PARP+ phenotype had longer overall survival (OS, log-rank p = 0.046). Overall, nine mutations were detected; M1 and M2 were completely new and M4, M7 and M8 were characterized as pathogenic. M7 and M8 were predominantly found in metastatic TNBC patients (p = 0.014 and p = 0.002). Thus, PARP-1 expression and increased mutagenic burden in TNBC patients’ CTCs, could be used as an indicator to stratify patients regarding therapeutic approaches.