The role of BRCA1-IRIS in the development and progression of triple negative breast cancers in Egypt: possible link to disease early lesion

BMC Cancer

Research Article

Danielle Bogan¹  Wael M. ElShamy²  Hend F. Yousef³  Lucio Meile⁴  Ahmed El Bastawisy⁵  Abeer A. Bahnassy⁶  Abdel-Rahman N. Zekri⁷ 

[1] Cancer Institute, University of Mississippi Medical Center, 2500 N. State Street, 39216, Jackson, MS, USA;Cancer Institute, University of Mississippi Medical Center, 2500 N. State Street, 39216, Jackson, MS, USA;Present Address: San Diego Biomedical Research Institute, 10865 Road to Cure, Suite 100, 92121, San Diego, CA, USA;Cytogenetics and Molecular Genetics, National Cancer Institute, Cairo University, Cairo, Egypt;Department of Genetics, Louisiana State University, Louisiana, USA;Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt;Molecular Pathology, National Cancer Institute, Cairo University, Cairo, Egypt;Virology and Immunology, National Cancer Institute, Cairo University, Cairo, Egypt;

关键词: Breast cancer;    Triple negative;    BRCA1-IRIS;    Metastasis;    Egypt;    Tumor-initiating cells;    Breast cancer early lesion;   

DOI  :  10.1186/s12885-017-3283-8

 received in 2016-10-19, accepted in 2017-04-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundBreast cancer is the most globally diagnosed female cancer, with the triple negative breast cancer (TNBC) being the most aggressive subtype of the disease. In this study we aimed at comparing the effect of BRCA1-IRIS overexpression on the clinico-pathological characteristics in breast cancer patients with TNBC or non-TNBC in the largest comprehensive cancer center in Egypt.MethodsTo reach this goal, we conducted an observational study at the National Cancer Institute (NCI), Cairo University (Cairo, Egypt). The data on all diagnosed breast cancer patients, between 2009 and 2012, were reviewed. BRCA1-IRIS expression measured using real time RT/PCR in these patients’ tumor samples was correlated to tumor characteristics, such as to clinico-pathological features, therapeutic responses, and survival outcomes.Results96 patients were enrolled and of these 45% were TNBC, and 55% were of other subtypes (hereafter, non-TNBC). All patients presented with invasive ductal carcinomas. No significant difference was observed for risk factors, such as age and menopausal status between the TNBC and the non-TNBC groups except after BRCA1-IRIS expression was factored in. The majority of the tumors in both groups were ≤5 cm at surgery (p = 0.013). However, in the TNBC group, ≤5 cm tumors were BRCA1-IRIS-overexpressing, whereas in the non-TNBC group they were BRCA1-IRIS-negative (p = 0.00007). Most of the TNBC patients diagnosed with grade 1 or 2 were BRCA1-IRIS-overexpressing, whereas non-TNBCs were IRIS-negative (p = 0.00035). No statistical significance was measured in patients diagnosed with grade 3 tumors. Statistically significant difference between TNBCs and non-TNBCs and tumor stage with regard to BRCA1-IRIS-overexpression was observed. Presence of axillary lymph node metastases was positively associated with BRCA1-IRIS overexpression in TNBC group, and with BRCA1-IRIS-negative status in the non-TNBC group (p = 0.00009). Relapse after chemotherapy (p < 0.00001), and local recurrence/distant metastasis after surgery (p = 0.0028) were more pronounced in TNBC patients with BRCA1-IRIS-overexpressing tumors compared to non-TNBC patients. Finally, decreased disease-free survival in TNBC/BRCA1-IRIS-overexpressing patients compared to TNBC/BRCA1-IRIS-negative patients, and decreased overall survival in TNBC as well as non-TNBC patients was driven by BRCA1-IRIS overexpression.ConclusionsTNBC/BRCA1-IRIS-overexpressing tumors are more aggressive than TNBC/BRCA1-IRIS-negative or non-TNBC/BRCA1-IRIS-overexpressing or both negative tumors. Further studies are warranted to define whether BRCA1-IRIS drives the early TNBC lesions growth and dissemination and whether it could be used as a diagnostic biomarker and/or therapeutic target for these lesions at an early stage setting.

【 授权许可】

CC BY   
© The Author(s). 2017