Association of CYP1A1 3801T>C Polymorphism with Pathological Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer: A Cross-Sectional Study Using Residual Cancer Burden

Abstract Background Triple-negative breast cancer (TNBC) still depends on cytotoxic neoadjuvant chemotherapy, yet pathological response varies widely between patients. Cytochrome P450 1A1 is expressed in breast tissue and metabolises xenobiotics locally, and its 3801T > C (M1, rs4646903) variant is more frequent in Asian populations. Its relationship with neoadjuvant chemotherapy response in TNBC has not been reported. Methods This analytic cross-sectional study aimed to test whether CYP1A1 3801T > C genotype is associated with pathological response, and included 98 women with TNBC treated with six cycles of neoadjuvant taxane–anthracycline chemotherapy followed by mastectomy at two tertiary referral hospitals in Indonesia between January 2022 and July 2025. CYP1A1 3801T > C was genotyped from formalin-fixed paraffin-embedded tumour DNA by polymerase chain reaction–restriction fragment length polymorphism using MspI. Pathological response was graded as Residual Cancer Burden (RCB) class 0 to III. Associations were tested with Fisher–Freeman–Halton exact tests and unadjusted proportional-odds ordinal logistic regression; clinicopathological predictors were assessed in a multivariable ordinal model. Results Genotype frequencies were TT 32.7%, TC 49.0% and CC 18.4% (C allele 42.9%, 95% confidence interval 36.1–49.9), consistent with Hardy–Weinberg equilibrium (p = 1.000). RCB class was 0 in 3.1%, I in 8.2%, II in 58.2% and III in 30.6%. Genotype was not associated with RCB class (p = 0.574): the odds ratio was 0.57 (95% confidence interval 0.25–1.32) for TC + CC versus TT, 0.60 (0.21–1.71) for CC versus TT + TC and 0.66 (0.37–1.17) per C allele. All three complete responders carried the C allele. Tumour size of 5 cm or more (odds ratio 4.29, 1.70–11.53) and lymphovascular invasion (odds ratio 4.68, 1.76–13.27) independently predicted a higher RCB class. Conclusions CYP1A1 3801T > C was not significantly associated with pathological response in TNBC, although imprecise estimates leave a smaller effect possible. Markers of tumour burden dominated response in this cohort, and larger prospective studies with germline genotyping are needed.