Krebswissenschaft und -therapie

The Role of PARP Inhibitors in the Treatment of Triple Negative Breast Cancer

Abstract

Karima Oualla, Lamiae Nouiakh, Otmane Zouiten, Mohamed Ismaili, lamiae Amaadour, Zineb Benbrahim, Samia Arifi and Nawfel Mellas

Triple Negative Breast Cancer (TNBC) is a particular subtype of breast cancer accounting for 15% to 20% of all breast cancer. It is defined on
immunohistochemistry (IHC) by negative estrogen receptor (ER) and progesterone receptors (PR) and negative human epidermal growth factor
receptor 2 (HER2) and characterized by aggressive nature, distinct metastatic patterns, lack of targeted therapies and poor outcomes. Cytotoxic
chemotherapy was the mainstay of treatment for long decades and the development of new treatments for selected patients was complicated
because of the heterogeneity of TNBC. The good understanding of molecular and genomic mechanisms of TNBC has allowed the development
of new targeted therapies more efficient. Although the heterogeneity of genetic alterations in TNBCs based on the ethnicity and the age, BRCA
mutations are found in around 20% to 25% of patients and especially in those of the basal-like immune-phenotype. Thus, targeting the defects
in the DNA repair pathway becomes a promising field of research for this selected category of TNBC patients. Poly (ADP-ribose) polymerase
(PARP) inhibitors exploit this DNA defects through synthetic lethality and therefore represent a promising treatment especially in BRCA1/ BRCA2
mutation carriers. These findings have finally allowed bringing personalized treatment to this orphan disease. In this work we tried to explain the
rationale and mechanisms of targeting the immune system in TNBC, to report the results from recent clinical trials that put immunotherapy as a
new standard of care in TNBC.