Background: Breast cancer has significantly increased in Arab populations, accounting for 13-30% of the newly diagnosed women malignancies. Neoadjuvant chemotherapy, including regimens based on cyclophosphamide, doxorubicin, and docetaxel, is effective for early-stage operable and locally advanced cancer.However, chemoresistance remains a major challenge. Therefore, we aimed to study FGFR2 (rs2981578) and FGFR4 (rs1966265) gene variants in predicting chemotherapy response in patients with locally advanced breast cancer.

Methods: This cross-sectional study involved 30 females with biopsy confirmed locally advanced primary breast cancer. Patients received neoadjuvant anthracyclin-cyclophosphamide-docetaxel-based regimens. Core biopsies were taken for histopathological diagnosis, and immunohistochemistry for HER2, PR, and ER was performed. Genotyping of FGFR2 and FGFR4 SNPs was performed using the TaqMan SNP genotyping assay. The RECIST criteria was used for assessment of treatment response.

Results: 66.7% of patients responded to chemotherapy, while 33.3% did not. Premenopausal patients showed a significantly higher response rate compared to menopausal patients (FEp=0.024). The distribution of FGFR2 and FGFR4 genotypes did not show significant difference between responders and non-responders. (FEp=1.000).

Conclusion: The G and A alleles of FGFR2 and FGFR4 variants were not associated with chemotherapy response in this study. Further research with larger cohorts is needed to validate our study results and identify other variants that would guide tailored management.