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Introduction: 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 the hereditary cases of breast cancer. According to the existing literature BRCA1 and BRCA2 associated breast cancer, it has been shown that BRCA associated breast cancers have different clinical, histological and immune-phenotypic features. To validate the effect of BRCA 1 or BRCA 2 germ line mutations on breast cancer aggressiveness and its impact on breast cancer clinical and histological features, we compared the histological, molecular status and clinical variables of 32 breast cancer patients with BRCA gene pathogenic mutations carriers and to the histopathological and molecular characteristics of 50 patients affected with breast cancer in the same age group but with no pathogenic mutations or variants of unknown significant (VUS) in either BRCA1 or BRCA2 genes. Methods: A retrospective study was conducted to study breast cancer cases that were evaluated at the hereditary breast and ovarian cancer clinic at the national center of cancer care and research (NCCCR) in the State of Qatar from 2013 to 2015. 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 to update the molecular data of those patients. Results: (82) patients with breast cancer were diagnosed at a young age (50 years of age and younger). (50) patients were BRCA negative and (32) patients were i positive. (22) Patients were found to have BRCA1 pathogenic mutations, (9) patients had BRCA2 pathogenic mutations and (1) patient carried pathogenic mutations in both BRCA1 and BRCA2 genes. Most patients had mutations in the BRCA1 with most mutations being small frame shift deletion or insertion in one or more exons that caused protein truncation. BRCA mutations was detected among women of younger ages. In terms of histopathology, the majority of BRCA associated breast cancers are invasive ductal carcinoma (IDC) detected in 94% with (74%) high nuclear grade 3/3, have a higher number of mitosis and show a high frequency of necrotic areas, and a higher proliferative rate and lymphocytic infiltration. All of these histopathological features point toward a more aggressive tumor type. In terms of immunohistochemical (IHC) tumor markers, triple negative detected in 56.3% accounted for most of the BRCA associated breast cancers. Triple positive accounted for 9.4%, followed by ER PR positive Her2 negative (34.4%) and ER PR negative Her2 positive (0%). Disease staging of all patients with breast cancer is done according to AJCC staging manual. Patients with BRCA pathogenic mutations diagnosed with stage II 60% followed by stage III 26.6% and stage IV14%. Patients with no pathogenic mutations in the BRCA genes also had IDC as being the most common histopathologcal type IDC 58% but also exhibited other type of histopathology such as ductal carcinoma in situ (DCIS) (10%), invasive lobular carcinoma (ILC) (6%), lobular carcinoma in situ (LCI). BRCA negative breast cancers exhibited 2% nuclear grade 3/3 in 36% of cases and high proliferative rate in 31%. Triple negative breast cancers accounted for 17%, triple positive 13%, ER PR positive Her2 negative 44% and ER PR negative Her 2 positive 13%. In terms of disease stage, those with no pathogenic mutations in the BRCA genes mostly had stage I 39% followed by stage II 61%, stag III 29%, and no cases were diagnosed with stage IV. Conclusion: These results suggest that breast cancers associated with BRCA mutations are more likely to be basal sub-type and exhibits more aggressive behavior, particularly in younger age groups and those patients present with a more advanced stage of disease than those with no pathogenic mutations in the BRCA genes who exhibit a less aggressive disease. We will continue to build our database for better characterization of our hereditary breast cancer cases at a clinical and molecular levels and use this information for future development of targeted anti-cancer agents use.

Qatar has one of the highest age-adjusted breast cancer incidences in the Arab world. Although this is much lower than the incidence in the West. Breast cancer incidence in Qatar was 45 per 100,000 in 2003-2007. 53 per 100,000 in 2008-2011. These higher incidence rates in Qatar are mainly due to the growing population. The prevalent age group, between both Qatari and non-Qatari patients, was 40-50 years old. This suggests that the age-specific incidence of breast cancer in Qatari women is shifting more to a pattern usually not seen in Western nations where median age at diagnosis is 61 years of age, moreover the diagnosis is often at advanced stages of breast cancer. These factors, together with reconfirmed evidence of mortality benefit from breast cancer screening trials, led to establishment the first hospital based mammographic breast cancer screening program in Qatar. It uses a distributed model of mammography service. The program accepts eligible asymptomatic women at age between 40-69 years and was launched in 2008. It adopted international standards of breast screening practice and breast cancer detection.