Abstract
Mortality rates from breast cancer in young women have fallen considerably in high-income countries but continue to rise in low-income countries such as Morocco. Young women with breast cancer face unique challenges due to the aggressive nature of the disease, the presence of aggressive subtypes (e.g., triple-negative, HER2-positive, and luminal B), and limited access to timely diagnosis and treatment. In addition, genetic factors play crucial roles in patient prognosis and response to treatment. The molecular landscape of breast cancer in young women has important implications for personalized medicine, such as the use of targeted therapies, namely poly (ADP-ribose) polymerase (PARP) inhibitors, which are particularly effective in patients with BRCA gene mutations. However, research into the genetic landscape of breast cancer in young women from low-income regions is limited, and the potential of personalized medicine to improve outcomes remains underexplored. This study aims to analyze the genetic landscape of breast cancer in young Moroccan women, with a focus on genetic alterations beyond the BRCA1 and BRCA2 genes. By expanding the panel of genes, we hope to identify other genetic variants that may influence the diagnosis, treatment, and follow-up of this high-risk population. Methods A retrospective study was conducted on 60 young women who were diagnosed with breast cancer between 2019 and 2024 at Hassan II University Hospital, Fez, Morocco. Genetic analysis was performed via next-generation sequencing (NGS) technology, specifically the Ion S5 sequencer and a custom-designed gene panel targeting 28 key genes associated with breast cancer and hereditary cancer syndromes. For statistical analysis, descriptive statistics were calculated for clinical variables (e.g., age, grades, molecular subtypes, genetic mutations). The correlation between genetic mutations and clinical outcomes was assessed using chi-square tests. All statistical analyses were performed using SPSS software. A significant level of p < 0.05 was used for all tests. Results The cohort had a mean age of 34.6 years, with 36.7% reporting a family history of cancer. DNA sequencing of the 60 patients yielded 15 pathogenic variants and 3 likely pathogenic variants; the genes involved being BRCA1, BRCA2, and ATM for the pathogenic variants, whereas for the likely pathogenic variants, the genes involved were MUTYH and APC, which suggests the presence of other potential genetic risk factors other than the BRCA1 and BRCA2 genes. Furthermore, the BRCA1 gene was mutated in 45% of patients with triple-negative breast cancer, highlighting the important role of genetic testing in identifying high-risk patients, which should greatly improve the management and treatment of the disease. Conclusion This study highlights the importance of genetic testing for personalized treatment of young breast cancer patients. Firstly, these results will help us to improve outcomes for young women with aggressive subtypes in low-income countries through the adaptation of targeted therapies such as PARP inhibitors. Secondly, this study will help us to identify at-risk family members, so that we can detect breast cancer at an early stage and adapt care accordingly. And finally, this study has allowed us to identify genes of interest other than the two BRCA1 and BRCA2 genes, demonstrating the diversity in this population.