Genotype and Phenotype Correlation of Breast Cancer in BRCA Carriers and Non-Carriers
Authors: Bugrein Hekmet , Bujassoum Salha Mohammed 
Published: July 2019

Breast cancer is both genetically and histopathologically heterogeneous disease, the biological basis for this heterogeneity is unknown, although there are some distinct phenotype-genotype correlations. Approximately 5% to 10% of breast cancer is hereditary and BRCA1 and BRCA2 genes are responsible for the majority of hereditary breast cancers. BRCA1 and BRCA2 mutant cells have defects in the DNA repair and chromosomal instability with marked defects in cell division [9]. In the literatures BRCA1 and BRCA2 associated breast cancers have different clinical, histological, immune-phenotypic features [6]. To validate the effect of BRCA 1 or BRCA 2 germ line mutation on breast cancer aggressiveness and on the clinical features, we analyzed, correlate the genotype, and compared histological and molecular status and clinical variables of 31 breast cancer patients with BRCA gene mutations carriers and histopathological and molecular characters of breast cancer in 50 patients affected in the same age group but with no pathogenic mutations or variants of unknown significant (VUS) in either BRCA1 or BRCA2 genes. This is a retrospective study and involved cases assessed on the hereditary breast and ovarian cancer clinic between 2013–2015 at the National Center of Cancer Care and Research (NCCCR) in the State of Qatar.MethodsA retrospective review of medical records was conducted to determine the clinical characteristics, the molecular results of BRCA testing and the tumor characteristics from the histopathology reports in addition to a new review of the tumor blocks. All of the cases were evaluated at the high risk hereditary breast and ovarian cancer clinic at the national center of cancer care and research (NCCCR) in state of Qatar between 2013–2015.Results(81) patients with breast cancers were diagnosed at ages 50 year and below, (50) patients were BRCA negative, and (31) patients were BRCA positive, (21) were BRCA1 mutation carriers, (8) patients were BRCA2 mutation carriers and (2) carried mutations in both BRCA1 and BRCA2 genes. On BRCA1,2 gene sequencing and MLPA the most detected mutation in BRCA gene is small frame shift deletion or insertion in one or more Exons, and protein truncation. In this study age group carriers and non-carriers are young (50 and below) but BRCA mutation detected with higher incidence in younger ages, Histopathology of invasive ductal carcinoma (IDC) was detected in (93.5%) of BRCA gene mutation carriers with (74%) high nuclear grade 3, and a higher proliferative rate were detected in non carriers control group nuclear grade 3 in 36% of cases and high proliferative rate in 31%. Triple negative (48.6%), Triple positive (16%), ER PR positive. Her 2 negative (26%) and ER PR negative Her 2 positive (9.6%) in BRCA carriers. In non carriers TN in 17%, triple positive 13%, ER PR positive Her 2 negative 44%, ER PR negative Her 2 positive 13%.ConclusionThese results suggest that tumors associated with BRCA mutations are more likely to be basal sub type, has more aggressive behavior (invasive, grade 3, Triple negative) affect younger age group, patient presented in more advanced stage further analysis needed to determined clinical outcomes in BRCA positive compare to control, in regards to local and systemic relapse, overall survival. however will continue to build up our data base for better characterization of our hereditary breast cancer cases at clinical and molecular level and use this information for future development of targeted anti-cancer agents use.