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 and BRCA2 variant landscape in Moroccan TNBC patients.
Methods: A retrospective cohort of Moroccan TNBC patients was evaluated using immunohistochemistry (IHC) to assess stromal tumor-infiltrating lymphocytes (TILs), programmed death-ligand 1 (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 and BRCA2 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 multiparametric immune and genomic profiling for improved risk stratification and support further investigation of population-specific immunogenomic patterns in North African TNBC patients.
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). doi: 10.1186/s43046-025-00295-x.
Fu L, Jiang Y, Wang C, Mei M, Zhou Z, Jiang Y, et al. A genome-wide association study on feed efficiency related traits in Landrace pigs. Front Genet. 2020;11. doi: 10.3389/fgene.2020.00692.
Gupta P, Bhalla AS, Thulkar S, Kumar A, Mohanti BK, Thakar A, et al. Neoadjuvant intra-arterial chemotherapy in advanced laryngeal and hypopharyngeal cancer. Asia Pac J Clin Oncol. 2013;12(1). doi: 10.1111/ajco.12123.
Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, 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, Jonas SF, Bataillon G, Criscitiello C, Salgado R, Loi S, et al. Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy. Ann Oncol. 2019;30(12):1941-1949. doi: 10.1093/annonc/mdz395.
Schwamborn K, Ammann JU, Knüchel R, Hartmann A, Baretton G, Lasitschka F, et al. Multicentric analytical comparability study of programmed death-ligand 1 expression on tumor-infiltrating immune cells and tumor cells in urothelial bladder cancer using four clinically developed immunohistochemistry assays. Virchows Arch. 2019;475(5):599-608. doi: 10.1007/s00428-019-02610-z.
Vennapusa B, Baker B, Kowanetz M, Boone J, Menzl I, Bruey JM, et al. Development of a PD-L1 complementary diagnostic immunohistochemistry assay (SP142) for atezolizumab. 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(14):1754-1760. doi: 10.1093/bioinformatics/btp324.
Danecek P, Bonfield JK, Liddle J, Marshall J, Ohan V, Pollard MO, et al. Twelve years of SAMtools and BCFtools. GigaScience. 2021;10(2). doi: 10.1093/gigascience/giab008.
Garrison E, Marth G. Haplotype-based variant detection from short-read sequencing. arXiv. 2012;arXiv:1207.3907. doi: 10.48550/arXiv.1207.3907.
Cingolani P, Platts A, Wang LL, Coon M, Nguyen T, Wang L, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff. Fly. 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(4):375-379. doi: 10.1007/s12254-020-00624-x.
Ezeome ER, Yawe KT, Ayandipo O, Badejo O, Adebamowo SN, Achusi B, et al. The African female breast cancer epidemiology study protocol. Front Oncol. 2022;12. 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. doi:10.11604/pamj.2025.50.105.43868.
Authors
Copyright (c) 2026 Archives of Breast Cancer
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright©. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International License, which permits copy and redistribution of the material in any medium or format or adapt, remix, transform, and build upon the material for any purpose, except for commercial purposes.