• PARP1 status in triple negative breast cancer and potential therapeutic opportunities
  • Sima Emadi Allahyari,1 Pantea Izadi,2,*
    1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences
    2. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences


  • Introduction: Breast cancer is the most frequently occurring cancer in women worldwide. Base on GLOBOCAN database, 11.6% of all cancers in 2018 are breast cancer which 6.6% leads to death. BRCA1 is a critical genes in breast cancer that can inactivated by different ways (hereditary mutation, promoter hyper methylation and epigenetics process). Inactivation of BRCA1 leads to abrupted Homologous Recombination Repair(HRR), this process is necessary to genome stability. When BRCA1 inactivation occur, other molecules could increased for compensate BRCA1 roles, such as PARP1. PARP1 is a enzyme that activated by DNA damage, which facilitate DNA repair in pathways involving single-strand breaks (SSBs) and base excision repair (BER). poly (ADP-ribose) polymerase 1 (PARP1) expression status plays a critical role in breast cancer progression and the clinical development of PARP1 inhibitors to treat breast cancer has advanced rapidly. Previous study on ovarian cancer with BRCA1 mutation indicate that in some patients redused expression of BRCA1 leads to increased expression of PARP1. Given to similar molecular process in ovarian cancer and breast cancer its possible that a similar phenotype could be identified and candidate in breast cancer for PARP inhibitors. Utilizing the concept of synthetic lethality has provided new opportunities for the development of targeted therapies, by allowing the targeting of loss of function genetic aberrations. In this cases cancer cell survival prevented by PARP inhibitors. So our purpose in this study was to find a subgroups of breast cancer base on molecular profiling is similar to ovarian tumors that responsing to PARP inhibitors.
  • Methods: BRCA1 and PARP1 expression evaluated in 62 tumor that divided two groups (Triple negative tumor and Non-triple negative tumor) by Real-time PCR.
  • Results: Statistical analysis (pearson correlation) showed that there was no correlation between BRCA1 and PARP1 expression in non-triple negative group but there was significant positive correlation between expression of these genes in triple negative group.Although in this study the relation between BRCA1 and PARP1 expression did not accordance with inherited ovarian cancer with BRCA1 mutation, but it is clear that molecular mechanisms are under way that lead to increased PARP1 expression. On the other hands in this study, there was no significant difference between relative expression of BRCA1 with subtypes (however the average expression of this gene in Non-triple negative subgroup was higher than TN subgroup.), but PARP1 expression in TN-subgroup was significantly higher than non-TN subgroups (P-value=0.004).
  • Conclusion: This study indicate that PARP1 expression increased in TN subtype. Since TN subtype doesn’t have targeted therapy options and doesn’t respond to targeted therapies (Herceptin and tamoxifen) , On the other hand because these tumors have poorer prognosis rather than other breast tumor , PARP inhibitors may be useful in this subtype.
  • Keywords: Breast cancer, triple negative, gene expression , BRCA1 and PARP1