IDENTIFICATION OF PARP1 AS A POTENTIAL THERAPEUTIC TARGET IN TRIPLE NEGATIVE AND BASAL-LIKE BREAST CANCER MOLECULAR SUBTYPES AMONG WEST ALGERIAN PATIENTS

Purpose: Breast cancer is partly responsible for the therapeutic failures of tumors with the most worsening prognoses. Increasing understanding of the cellular aberrations inherent to cancer cells was an important step towards therapy individualization. Poly (ADP-ribose) polymerase-1 (PARP1) as a promising novel target in breast cancer was an example of this strategy. However, the biological and clinical significance of PARP1 expression and its associations with outcome remain to be defined. We aimed in present study to explore PARP1 expression in breast cancers samples among west Algerian patients.

Materials and Methods: We classified 78 primary breast cancers collected and diagnosed at the Regional Military Hospital of Oran (Algeria) using immunohistochemical biomarkers then; we examined immunohistochemical PARP1 expression and assessed its correlation with clinicopathological parameters and breast cancer molecular subtypes.

Results: PARP1 nuclear overexpression was found in (44, 8%) of all infiltrating breast carcinomas. PARP-1 protein overexpression was associated to higher tumor grade (P=0.036), hormone-negative tumors (P=0.005) and estrogen-negative tumors (P=0.003). Moreover, PARP1 was significantly expressed in Triple-negative (P=0.015) and basal-like breast cancers, but was also present in HER2 positive breast cancers (P=0.014).

Conclusions: Our data highlights the interest of immunohistochemical biomarkers in breast cancer molecular classification. We found that PARP1 overexpression is associated with triple-negative and basal-like tumors and could be a potential therapeutic in these two pejorative breast cancer subtypes. Furthermore, PARP1 overexpression could be a predictive biomarker of therapeutic resistance in HER2 positive tumors.The assessment of PARP1 protein expression may improve the selection of patients for PARP1 inhibitor therapy.