Abstract
AIMS: Sequential Anthracycline-Taxane chemotherapy is standard treatment for BC. This study examines the combined impact of low BMI and CYP polymorphisms on treatment response. METHOD: BMI was assessed before chemotherapy, and clinical response was evaluated using RECIST v.1. Four SNPs in CYP2C9, CYP2C19, and CYP3A4 gene were analyzed in 148 samples using PCR-RFLP. RESULTS: CYP2C19 (G681A) was significantly associated with treatment non-responsiveness in all genetic models namely dominant (OR11.119; 95%CI [5.103-24.228], p < 0.0001), recessive (15.818; [4.548-55.015]; p < 0.0001), codominant (χ(2) 48.229; p < 0.0001). No significant association was found in other two genes CYP2C9 (C430T, A32621C) and CYP3A4 (A392G). When combined with BMI, the CYP2C19 AA genotype showed significant associations with poor treatment response for low BMI group across all genetic models: dominant (9.60; [2.892-31.864]; p < 0.0001), recessive (1.473; [1.404-2.164]; p < 0.001), and codominant (χ(2) 18.897; p < 0.0001) and AA associated with lowest PFS: 38 months; HR >1. OS (39.79 months; p = 0.039) were lowered among GA genotype with increased HR (HR 3.78; p = 0.031). CONCLUSION: AA genotype at G681A in low BMI patients showed the poorest chemotherapy response and lowest PFS (HR>1). CYP2C19 variants (AA) may serve as predictive markers for non-responsiveness towards AC-T chemotherapy in low BMI BC patients, highlighting the need for genetic counselling and nutritional support to improve treatment outcomes.