Harnessing genomic profiling for precision breast cancer therapies: Advances in HER2-targeted treatments, PARP inhibitors for BRCA mutations, and insights from clinical trials

The therapeutic landscape for breast cancer has evolved considerably over time; specifically, the integration of genomic profiling and molecular genetics has improved personalized therapeutic strategies. Genomic profiling identifies mutations and allelic variations in breast cancer, enabling more targeted interventions. Genetic research has highlighted the overexpression or dysfunction of the HER2 receptor, ALKBH5 enzyme, BRCA proteins, and PARP enzymes in advanced breast carcinomas. Current treatment modalities include HER2-targeted agents and PARP inhibitors. The application of monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs) to target overexpressed HER2 receptors in oncology patients has improved survival outcomes and treatment responses. In addition, ADCs have shown remarkable efficacy by selectively targeting cancer cells while sparing healthy tissue, utilizing target-specific monoclonal antibodies conjugated to cytotoxic payloads. Conversely, PARP inhibitors are primarily indicated for triple-negative breast cancer (TNBC) cases due to the high prevalence of BRCA1/BRCA2 mutations that impair DNA repair mechanisms. This review provides a comprehensive analysis of breast cancer treatments and associated clinical trials, including genomic profiling and drugs targeting the HER2 receptor [mAbs, ADCs, and TKIs] and PARP inhibitors. Furthermore, we examine the effect of these therapeutic agents on BRCA1/2 mutations and other relevant enzymatic pathways. Despite these advancements, certain challenges persist, such as the emergence of drug resistance, underscoring the need for further research and innovative techniques to overcome these limitations.