Abstract
BackgroundTriple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, that represents 10–20% of all breast carcinomas and characterized by the lack of a specific cell surface marker compared to other breast cancer subtypes. Due to the absence of molecular markers for TNBC his treatment options remains limited, without proven targeted therapies, which emphasize the need for discovering molecular markers that could be targeted for patient treatment, An important number of TNBC cases harbor aberrations in the phosphoinositide 3-kinase (PI3K) pathway, leading to constitutive activation of the downstream signaling pathway. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (~ 30%) observed, along with protein loss of PTEN and AKT activation by phosphorylation (pAkt). Therefore, we propose to analyze clinocopathologic and molecular characteristics of PI3K/AKT/PTEN pathway in Moroccan triple negative breast cancer patients.MethodsWe conducted a retrospective study of 39 patients diagnosed with triple negative breast cancer between early 2013 and 2016. In this study, we used the Ion Personal Genome Machine (PGM) and Ion Torrent Ampliseq Cancer panel to sequence hotspot regions from PIK3CA, AKT and PTEN genes to identify genetic mutations in 39 samples of TNBC subtype from Moroccan patients and to correlate the results with clinical-pathologic data.ResultsAll patients were female with a median age of 46 years from (34–65). Most patients have had invasive ductal carcinoma (84.6%) and 69.2% of them were grade III SBR. Among the 39, 9 were right sided tumor patients and the remaining 30 were left-sided. Mutational analysis of PIK3CA gene was achieved in all TNBC patients. PIK3CA hotspot mutations were detected in 5/39 of TNBC (13%), in detail, among these 5 TNBC patients, one harbored mutation in exons 9 and four in exon 20.ConclusionThe PI3KCA gene is highly activated and plays a crucial role in the pathogenesis of TNBC more, therefore, may be a potential therapeutic target to improve outcomes in patients.
Highlights
Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, that represents 10–20% of all breast carcinomas and characterized by the lack of a specific cell surface marker compared to other breast cancer subtypes
Since the development of molecular technologies tell many genomic studies has been conducted in purpose of better understanding the molecular nature of triple negative breast cancer, these studies have shown that TNBC could be classified into numerous independent subtypes remarkably heterogeneous at the genomic level [6], They further shed light into the large number of genes and major cellular pathways potentially involved in TNBC tumorigenesis
TNBC samples were characterized by Estrogen Receptor (ER), Progesterone Receptor (PR), and HER2 negativity, with ki67 proliferation index ranging from 30 to 90%
Summary
Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, that represents 10–20% of all breast carcinomas and characterized by the lack of a specific cell surface marker compared to other breast cancer subtypes. We propose to analyze clinocopathologic and molecular characteristics of PI3K/AKT/PTEN pathway in Moroccan triple negative breast cancer patients. Jouali et al BMC Cancer (2018) 18:900 cells is crucially required to improve TNBC patients outcome [5]. This emphasize the importance of molecular studies in this breast cancer subtype. Since the development of molecular technologies tell many genomic studies has been conducted in purpose of better understanding the molecular nature of triple negative breast cancer, these studies have shown that TNBC could be classified into numerous independent subtypes remarkably heterogeneous at the genomic level [6], They further shed light into the large number of genes and major cellular pathways potentially involved in TNBC tumorigenesis. There has been intensive research to define the relative contributions of these genes and cellular pathways in TNBC and to identify therapeutic targets for TNBC based on genomics [7]
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