Prevalence Of BRCA1 Germline Mutations Research Articles

Abstract 271: Clinicopathological and molecular study of breast cancer in Algerian women from the Aures region: Data from the anti-cancer center of Batna

Abstract Background:Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. The aim of this study was to analyze the different proportions and distribution of breast cancer molecular subtypes and to determine their associations with some clinical and pathological characteristics in women from the Aures region. We also screened for the prevalence of BRCA1 germline mutations in HBOC patients. Materials and Methods: Clinical and tumor characteristics data of 1144 breast cancer patients were collected from cancer registry of anticancer center of Batna. Breast cancers were diagnosed between 2011 and 2015. Breast cancer subtypes definitions were as follow: Luminal A (ER+ and/or PR+,HER2-), Luminal B (ER+ and/or PR+,HER2+),TNBC (ER-, PR-,HER2-) and HER2+ (ER-, PR-, HER2+). We also compared patients with TNBC and those with other breast cancer subtypes. Differences between the two groups with regard to clinicopathologic parameters: age at diagnosis, menopausal status, histological type, histological grade, breast feeding and oral contraception were examined using Chi square test. BRCA1 was screened by PCR direct sequencing in 22 HBOC patients including all exons where a mutation was previously found in Algerian population (exons 3, 5, 11). Results: The mean age at diagnosis cancer was 48.5 years. Proportions of luminal A, luminal B, TNBC and HER2+ breast cancer subtypes were 47.29%, 21.94%, 21.24% and 9.52%, respectively. We noted a significant difference in the distribution of age at diagnosis among the four cancer subtypes (P = 0.04). Invasive Ductal Carcinoma was the most common histological type in all breast cancer subtypes. Tumors with histological grade 2 and 3 were more common in patients for the four breast cancer subtypes. Our data showed significant differences between premenopausal and postmenopausal status (P=0.00) and tumor histological grade (P<0.03) between TNBC and non TNBC patients. The proportion of premenopausal status was higher in TNBC and non TNBC. Among tumor with histological grade III, TNBC accounted for 33.33% for all TNBC patients and non TNBC accounted for 30.23% for all non TNBC patients. The three BRCA1 recurrent mutations c.83_84delTG, c.181T>G and c.798_799delTT have not been detected in our present study. Conclusion: We report here for the first time, the distribution of molecular subtypes of breast cancer and some clinical and pathological characteristics in a cohort of female breast cancer patients from the Aures region. Interestingly, the proportion of TNBC subtype in women found in our study is similar to African-American breast cancer patients and higher than reported in white women in Europe and America. Further studies are needed to determine the outcome of the different breast cancer subtypes in the Aures region. Large studies of the screening of BRCA1 and BRCA2 genes are on going for the implementation of the genetic testing. Citation Format: Farid Cherbal, Chiraz Mehemmai, Khadidja Gassi, Abdelmoumene Guedioura, Yosr Hamdi, Wassila Benbrahim, Rabah Bakour. Clinicopathological and molecular study of breast cancer in Algerian women from the Aures region: Data from the anti-cancer center of Batna [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 271. doi:10.1158/1538-7445.AM2017-271

Abstract 2553: Prevalence of BRCA1 germline mutations in Algerian population: implications for genetic testing and counseling

Abstract Background: Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women.In this study, we estimated the prevalence of BRCA1 germline mutations in 192 patients with hereditary breast and/or ovarian cancer and sporadic triple-negative breast cancer, respectively. Materials and Methods: 192 Patients and their families were referred through several public hospitals and private medical clinics which provide oncology services throughout Algeria. Patients were selected for family history of breast and/or ovarian cancer. In addition, in the present study, all women (age under 50 years) with triple-negative breast cancer (TNBC) were considered eligible. BRCA1 was screened by PCR-direct sequencing in all patients including all exons where a mutation was previously found in Algerian population (exons 2, 3, 5 and 11). Results: The analysis of DNA samples of 192 individuals revealed that 11 patients carried pathologic germline mutations in BRCA1 gene (5.7%).Five distinct pathogenic mutations: c.19_47del, c.83_84delTG, c.181T>G, c.798_799delTT and c.2125_2126insA were indentified. Interestingly, the BRCA1 mutation c.83_84delTG detected in previous studies in two unrelated Algerian breast cancer families has been identified in this study in 4 patients with a frequency of 2% (4/192): 3 TNBC patients and one patient with a bilateral ovarian cancer, respectively. The four patients had a strong hereditary breast and/ or ovarian cancer history. The c.181T>G/p.Cys61Gly mutation has been detected here in two young breast cancer patients, a bilateral breast cancer patient with a family history of breast cancer and a young TNBC patient (diagnosed at age 36 years), respectively. To date, the Cys61Gly pathogenic variant is one of the most frequent founder mutation identified in Central European populations, has been previously reported for the first time in two Algerian and Moroccan families. The BRCA1 mutation c.798_799delTT was identified here in a young TNBC patient with a family history of breast cancer. Interestingly, this mutation has been previously detected in several unrelated families from Algeria, Tunisia, Morocco and Italy, respectively. As Mediterranean countries share a common history and migration flow history, BRCA1 mutation c.798_799delTT could be a Mediterranean founder mutation. The BRCA1 mutation c.2125_2126insA has been detected here for the first time in three young TNBC patients with a family history of breast cancer and prostate cancer. Conclusions: The accumulating knowledge about the prevalence and nature of BRCA1 mutations in Algerian population and the identification of specific mutations will contribute in the future to the implementation of genetic testing and counseling for families at risk. Based on our currents results, we recommend using the TNBC immunophenotype as criterion to screen for BRCA1 germline mutations in patients with early onset breast cancer. Citation Format: Farid Cherbal, Hadjer Gaceb, Chiraz Mehemmai, Rabah Bakour, Kamelia Yatta, Ikram Boukoufa, Hassen Mahfouf, Kada Boualga. Prevalence of BRCA1 germline mutations in Algerian population: implications for genetic testing and counseling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2553.

Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC)

BRCA1-associated breast cancers have been associated to a triple-negative phenotype. The prevalence of BRCA1 germline mutations in young onset TNBC based on informativeness of family history has not been reported. From January 2008 to May 2009 were collected blood and tumor samples from patients with TNBC younger than 50 years and without a family history of breast and ovarian cancer in first- and second-degree relatives. Analysis of BRCA1 germline mutations was made. Age at diagnosis and informativeness of family history (presence of female in first- and second-degree relatives alive until age 45) was collected in all cases. Immunohistochemistry of basal-like features was performed centrally in all available tumors. Seven pathogenic mutations were detected in 92 patients (7.6 %), two of them in patients younger than 35 years (28.6 %) (Fisher's exact test, p = 0.631). Three non-classified variants were detected (3.2 %). Family history was informative in two patients with a pathogenic mutation (28.6 %) and not informative in five (71.4 %) (Fisher's exact test, p = 0.121). Of the seven patients with a pathogenic mutation, four had a basal-like phenotype. Patients with apparently sporadic TNBC younger than 50 years and a non-informative family history are candidates for germline genetic testing of BRCA1.

HER-2/neu status and tumor morphology of invasive breast carcinomas in Ashkenazi women with known BRCA1 mutation status in the Ontario Familial Breast Cancer Registry.

The prevalence of BRCA1 germline mutations is greater in the Ashkenazi Jewish population than in the general North American population. The Ontario Familial Breast Cancer Registry collects clinical and family history data in familial breast carcinoma cases, and unselected Ashkenazi breast carcinomas, and acts as a tumor tissue repository. Using this resource, we examined the tumor morphology, hormone receptor status, and HER-2/neu protein overexpression in Canadian Ashkenazi breast carcinoma patients whose germline BRCA1 mutation status is known. Thirty-eight tumors from 32 BRCA1 carriers and 354 tumors from 334 noncarriers were analyzed. The tumors in BRCA1 mutation carriers were more likely to be high grade (P < 0.0001) and estrogen receptor negative (P < 0.004). There was an increased frequency of typical medullary carcinomas in mutation carriers when all tumors were analyzed. However, this difference did not remain statistically significant when only the first tumor diagnosed in each patient was included in the analysis. There was no difference in HER-2/neu protein overexpression between the two groups overall (P = 0.07). However, when the analysis was restricted to Grade III tumors, there were significantly fewer HER-2/neu-positive tumors in the mutation carriers versus noncarriers (3.1% vs. 21.5%, P = 0.012). No significant differences were found in the incidence of lymph node status, progesterone receptor status, lymphatic vessel invasion, degree of lymphocytic infiltration, or in the presence of ductal carcinoma in situ associated with the invasive tumors. Increasing awareness of the morphologic and immunophenotypic features more commonly found in BRCA1-associated breast carcinomas may lead to a wider use of these characteristics in genetic screening programs and provide further clues to their pathogenesis.