Personalized medicine in Triple-Negative Breast Cancer: Combining Neoantigen Vaccination and Genomic Profiling in a patient Undergoing Neoadjuvant Chemotherapy

Laura Martinez¹David Andres Bernal-Estévez²Daniel Stiven Alzate-Gutierrez³Diego Alfredo Amaya-Ramirez³Oscar Iván Reyes-Cortés⁴CARLOS A PARRA-LOPEZ^1*

• ¹Immunology and Translational Medicine Research Group, Department of Microbiology, Medical School, Universidad Nacional de Colombia, Bogota, Colombia
• ²Immunology and Clinical Oncology Research Group, Fundacion Salud de Los Andes, Bogotá, Colombia
• ³Immunology and Translational Medicine Research Group, Department of Microbiology, Medical School, Universidad Nacional de Colombia, Bogotá, Colombia
• ⁴Hospital Universitario Nacional, Corporacion UN, Medical School, Universidad Nacional de Colombia, Bogotá, Colombia

Triple-negative breast cancer (TNBC) is an aggressive form of cancer with the worst prognosis among all breast cancer subtypes. The limited effectiveness of first-line treatments, such as systemic neoadjuvant chemotherapy (NAC) and surgery, emphasizes the urgent need for alternative therapies. Next-generation sequencing (NGS) has revolutionized precision oncology by enabling the identification of tumor-specific neoantigens for personalized vaccines and profiling actionable mutations for targeted treatments. However, the usefulness of these methods in TNBC, especially in the context of NAC, remains largely unexplored. Here, we present a case of a TNBC patient treated with NAC combined with dendritic cells (DCs) pulsed with a personalized tumor neoantigen. Whole-exome sequencing (WES) of both germline and tumor tissue, along with tumor RNA sequencing (RNA-Seq), enabled us to identify neoantigens for vaccine development. Selected neoantigens elicited an IFN-γ response in peripheral blood mononuclear cells (PBMCs) before vaccination, indicating pre-existing immunity. After vaccination, the immunogenicity of the neoantigens was demonstrated by increased IFN-γ secretion, upregulation of activation markers CD69 and CD154 on CD8⁺ and CD4⁺ T cells, and polyclonal expansion of TCR-CDR3 after peptide stimulation. Interestingly, an immune response against a non-vaccine neoantigen was observed following immunization. While this supports the possibility of epitope spreading, the responses observed in pre-vaccination samples prevent us from attributing this effect solely to the vaccination. Germline WES identified a splice-altering pathogenic variant in ATM (c.2250G>A, p.Lys750=), confirming hereditary cancer predisposition. Somatic mutation analysis revealed alterations in TP53 (p.Gly199Ter), NF1 (p.Phe1593SerfsTer31), and PIK3CA (p.Glu542Lys), all supported by OncoKB level-1 evidence. This case highlights the potential of integrating precision oncology for TNBC patients undergoing NAC by detecting inherited risks, identifying actionable targets, and providing personalized neoantigen-based immunotherapy. However, as a single-patient case, these findings are preliminary and require validation in larger cohorts.