Immunogenomic Characterization of Triple-Negative Breast Cancer in a Moroccan Cohort and Its Prognostic Implication Immunogenomics TNBC
Abstract
Background: In North Africa, triple-negative breast cancer (TNBC) is a highly prevalent, aggressive, and diverse disease with unique clinical features. In this population, the prognostic significance of immune infiltration and genomic changes is still not fully understood. In order to investigate their relationships with relapse-free survival, this study sought to provide an integrated analysis of the tumor immune microenvironment and BRCA1/2 variant landscape in Moroccan TNBC patients.
Methods: A retrospective cohort of Moroccan TNBC patients was evaluated using immunohistochemistry to assess stromal tumor-infiltrating lymphocytes (TILs), PD-L1 expression, and immune cell subsets (CD3, CD4, CD20, and CD56). Targeted next-generation sequencing of BRCA1 and BRCA2 was performed on tumor tissue. Associations between immune biomarkers, genomic variants, and clinical outcomes were analyzed using appropriate statistical and bioinformatic approaches.
Results: The cohort exhibited significant heterogeneity in immune infiltration and advanced disease at diagnosis. Higher stromal TIL levels were observed in patients without relapse, although this association did not reach statistical significance in the present cohort. BRCA1/2 variants were frequently detected and showed heterogeneous immune profiles across tumors. Limited redundancy among immune markers was found in correlation analyses, suggesting that these markers may capture complementary aspects of the immune microenvironment.
Conclusion: This integrated immunogenomic analysis suggests the potential prognostic relevance of the tumor immune microenvironment in Moroccan TNBC patients. The findings emphasize the value of multi-parametric immune and genomic profiling for improved risk stratification and support further investigation of population-specific immunogenomic patterns in North African TNBC patients.
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References
Gaceb H, Cherbal F, Bakour R, Ould-Rouis A, Mahfouf H. Clinicopathological and Molecular Study of Triple-Negative Breast Cancer in Algerian Patients. Pathol Oncol Res. 2018;24(2):297–308. doi:10.1007/s12253-017-0242-2
Laraqui A, Uhrhammer N, Lahlou O, et al. Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population. Int J Med Sci. 2012;10(1):60–67. doi:10.7150/ijms.3648
Essalihi A, Bouchra O, Khadiri K, Khadrouf Z, Karkouri M. Immunotherapy for triple-negative breast cancer: current trends and future prospects. J Egypt Natl Canc Inst. 2025;37(1):51. doi:10.1186/s43046-025-00295-x.
Mighri N, et al. Identification of novel BRCA1 and RAD50 mutations associated with breast cancer predisposition in Tunisian patients. Front Genet. 2020;11:692. doi:10.3389/fgene.2020.00692
Fourati A, Boussen H, El May MV, et al. Descriptive analysis of molecular subtypes in Tunisian breast cancer. Asia-Pac J Clin Oncol. 2014;10(4):317–325. doi:10.1111/ajco.12123
Salgado R, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: Recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259–271. doi:10.1093/annonc/mdu450
Park JH, et al. Prognostic value of tumor-infiltrating lymphocytes in early-stage triple-negative breast cancer without adjuvant chemotherapy. Ann Oncol. 2019;30(12):1941–1949. doi:10.1093/annonc/mdz395
Schwamborn K, et al. Multicentric comparability study of PD-L1 expression assays in urothelial bladder cancer. Virchows Arch. 2019;475(5):599–608. doi:10.1007/s00428-019-02610-z
Vennapusa B, et al. Development of a PD-L1 complementary diagnostic IHC assay (SP142). Appl Immunohistochem Mol Morphol. 2019;27(2):92–100. doi:10.1097/PAI.0000000000000594
Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016;13(11):674–690. doi:10.1038/nrclinonc.2016.66
Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–2120. doi:10.1093/bioinformatics/btu170
Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25(13):1754–1760. doi:10.1093/bioinformatics/btp324
Danecek P, et al. Twelve years of SAMtools and BCFtools. GigaScience. 2021;10(3):giab008. doi:10.1093/gigascience/giab008
Garrison E, Marth G. Haplotype-based variant detection from short-read sequencing. arXiv. 2012; arXiv:1207.3907.
Cingolani P, et al. A program for annotating and predicting SNP effects, SnpEff. Fly (Austin). 2012;6(2):80–92. doi:10.4161/fly.19695
McLaren W, et al. The Ensembl Variant Effect Predictor. Genome Biol. 2016;17(1):122. doi:10.1186/s13059-016-0974-4
Bartl T, Farr A. Homologous recombination deficiency in breast cancer. memo. 2020;13:375-379. doi:10.1007/s12254-020-00624-x.
Ezeome ER, et al. The African Female Breast Cancer Epidemiology Study Protocol. Front Oncol. 2022;12:856182. doi:10.3389/fonc.2022.856182
Lam BM, Verrill C. Clinical significance of tumour-infiltrating B lymphocytes in breast cancer: a systematic literature review. Front Immunol. 2023;14:1109675. doi:10.3389/fimmu.2023.1109675
Khadiri K, Khadrouf Z, Mellouki A, Bouchra O, Essalihi A, Naya A, et al. Epidemiological and molecular profile of breast cancer: a retrospective study in Casablanca, Morocco. Pan Afr Med J. 2025;50(105). doi:10.11604/pamj.2025.50.105.43868.
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