For the first time, we report the distribution of molecular breast cancer subtypes and their associations with some clinicopathological characteristics in a large cohort of Algerian women. In our current study, the median age of diagnosis for all breast cancer subtypes was younger than the average age in Europe and America. Luminal A was the most common sub- type in our patients followed by TNBC. The proportion of luminal A subtype was lesser than reported in white women with breast cancer in Europe and America. The proportion of TNBC subtype in Algerian women was higher compared with Caucasian women of European ancestry. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for Algerian breast cancer patients.

Triple-negative breast cancer (TNBC) is associated with aggressive tumor behavior, poor prognosis and BRCA1 mutations. There are limited data regarding TNBC among Algerian women. In this study, we sought to determine clinical and tumor characteristics associated with TNBC. We also screened for the prevalence of BRCA1 mutations in unselected cohort of TNBC patients. Clinical and tumor characteristics data of 877 breast cancer patients diagnosed between 2011 and 2015, were collected from cancer registry of public hospital of Rouiba. Patients were divided in two groups: those with TNBC and those with other breast cancer subtypes. Differences between the two groups with regard to clinical and tumor characteristics were compared using Fisher's exact test. BRCA1 mutations analysis was performed in unselected cohort of 103 women with TNBC, including all exons where a mutation was previously found in Algerian population (exons 2, 3, 5, 11). The median age at diagnosis for TNBC and non-TNBC patients was 47.4 years and 49.4 years, respectively. The proportion of TNBC was 19.95%. Our data showed significant differences in menopausal status, TNM stage, histological type, tumor histological grade, Ki67 expression and family history of breast cancer between TNBC and non-TNBC patients. Four distinct deleterious mutations in BRCA1 gene were detected in eight young TNBC patients. TNBC is associated with young age, poor histopathological characteristics and family history of breast cancer. BRCA1 mutations have been detected in young TNBC patients. TNBC phenotype should be added as criterion to screen for BRCA1 mutations in Algerian women.

Background: Breast cancer is the most commonly diagnosed cancer and the leading cause of morbidity and mortality among Algerian women.The objective of this retrospective cohort study was to analyze some clinicopathological and molecular characteristics of breast cancer diagnosed between 2011 and 2019. Here we also report the experience of our research laboratory for the screening of BRCA1 and BRCA2 genes in hereditary breast and ovarian cancer (HBOC) patients. Materials and Methods: The population study included 7655 consecutive breast cancer patients. Data were collected from cancer registries of three medical oncology services and two anti-cancer centers located in north central region and eastern region of Algeria, respectively. Breast cancers were diagnosed between 2011 and 2019. Patient and tumor information included: age at diagnosis, menopausal status, receptor status, Ki-67 score, histological type,TNM stage and histological grade. Recurrent germline mutations on BRCA1 and BRCA2 genes previously found in Algerian patients were screened using PCR-Sanger sequencing in 230 HBOC patients. In addition, 18 HBOC patients were analyzed by NGS using a cancer panel of 30 hereditary cancer genes or BRCA1/2 genetic test. Results: The median age at diagnosis of the patients was 49.52 years. Data for age at diagnosis were available for 7389 patients. 55.29% patients were diagnosed under the age of 50 years and 55.83% had a premenopausal status. Data for receptor status were available for a total of 5599 patients. Of these, 55.75% patients were luminal A, 19.79% were TNBC, 17.39% were luminal B and 7.05% were HER2+. Data for Ki-67 score were available for 3357 cases. We noticed that 62.73% patients had a Ki-67 score ≥ 20% and 37.27% had a score <20%. Data for histological tumor type were available for 6145 cases. 84.28% patients had invasive ductal carcinoma followed by 8.84% with invasive lobular carcinoma. Data for TNM stage were available for 3524 cases. We identified 59.3% patients with stage III, 22.3% with stage II and 9.5% with stage IV. Data for histological grade were available for 6693 patients. We found 67.45% patients with grade II and 25.51% with grade III, respectively. 10 distinct BRCA1 germline mutations have been detected in 18 families and 5 distinct BRCA2 germline mutations have been identified in 5 families. The BRCA1 recurrent mutation c.83_84delTG has been detected in 5 unrelated families.The BRCA1 recurrent mutation c.2125_2126insA has been identified in 3 unrelated families. In addition, the BRCA1 c.181T>G has been found in two unrelated families. Interestingly, our results also showed differences in the distribution of the mutation spectrum of BRCA1 and BRCA2 genes between the eastern region and the north central region of Algeria. Conclusion: Our current study will contribute in developing optimal clinical trial protocols and personalized management strategies for breast cancer patients. Citation Format: Farid Cherbal, Leticia Ledmila Saada, Massila Nehar, Kamelia Yatta, Lydia Souha Zerrouki, Wafa Abdou, Chiraz Mehemmai, Hadjer Gaceb, Wassila Benbrahim, Hassen Mahfouf, Kada Boualga. Clinicopathological and genetic features of breast cancer in Algerian population: A multicenter study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 887.

Background: Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. To date, triple negative breast cancer (TNBC) shows substantial overlap with basal type cancer and it is associated with aggressive tumor behavior, poor prognosis and BRCA1 mutations. In the present study, we screened for the prevalence of BRCA1 and BRCA2 germline mutations in a cohort of 169 TNBC patients using PCR-Sanger sequencing and NGS with a cancer panel of 30 hereditary cancer genes or BRCA1/BRCA2 genetic test. Materials and Methods: 169 TNBC patients and their relatives were referred trough several public hospitals from six years (2013-2019). BRCA1 germline mutation was screened using PCR-Sanger sequencing in 66 TNBC patients with strong family history of breast and ovarian cancer and 103 sporadic TNBC patients including all exons where a mutation was previously found in Algerian population (exons 2, 3, 4, 10, 17 and 19). BRCA2 germline mutation was screened using PCR-Sanger sequencing in 24 TNBC patients with strong family history of breast cancer including all exons where a mutation was previously found in Algerian patients (exons 10 and 22). In addition, nine (9) TNBC patients with strong family history of breast and ovarian cancer were analyzed by NGS using BRCA1 and BRCA2 test or a cancer panel of 30 hereditary genes (Colors genomics). Results: The analysis of the genomic DNA samples of 169 TNBC patients revealed that 15 patients carried pathogenic germline variants in BRCA1 gene and three patients carried pathogenic variants in BRCA2 gene (10.65%). Eight distinct germline mutations in BRCA1 have been detected in this study: c.83_84delTG, c.181T>G, c.798_799delTT, c.505C>T, c.923_924delGC, c.2125_2126insA, c.5257A>G and deletion of exon 15. Interestingly, the recurrent and specific mutation c.83_84delTG has been detected in 4 unrelated TNBC patients. The pathogenic variant c.2125_2126insA has been detected in three unrelated families and also in the first relatives of 2 patients. The rare likely pathogenic variant BRCA1 c.5257A>G/p.Arg1753Gly has been detected in young female TNBC patient. The Del exon 15 in BRCA1 has been detected in two unrelated patients. Three distinct germline mutations in BRCA2 have been detected in three TNBC patients: c.1813dupA, c.7654dupA and c.8485C>T. Interestingly, these three mutations are reported for the first time in Algerian population. The c.1813dupA and c.8485C>T pathogenic variants have been detected in two young female TNBC patients with a family history of male breast cancer. Conclusions: In the current study, we detected recurrent germline mutations in BRCA1 gene in early onset TNBC patients. BRCA2 pathogenic variants have also been detected in young female TNBC patients. TNBC immunophenotype should be considered as an additional criterion for genetic counselling and testing of BRCA genes in Algerian women with early onset breast cancer. Citation Format: Farid Cherbal, Chiraz Mehemmai, Hadjer Gaceb, Hassen Mahfouf, Kada Boualga. BRCA1 and BRCA2 germline mutational spectrum in Algerian triple negative breast cancer (TNBC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1451.