Impact of ABCB1 polymorphisms on response to anthracycline chemotherapy in breast cancer patients

Vollständiger Abstract

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Abstract Breast cancer is the most prevalent cancer in women, and anthracycline-based chemotherapy, such as doxorubicin, is one of the main treatments. Unfortunately, treatment response varies between individuals, and drug resistance continues to limit the effectiveness of breast cancer treatment. Genetic differences, including single nucleotide polymorphisms (SNPs), in the ATP-binding cassette subfamily B member 1 (ABCB1) gene, which encodes the efflux transporter P-glycoprotein, are believed to modify the level of drug accumulation in cells and alter chemotherapy effect. This cohort study recruited 122 breast cancer patients who were all receiving doxorubicin-based chemotherapy. Participants were genotyped for three common ABCB1 SNPs: C3435T , G2677A/T , and C1236T . Our findings indicate that patients aged 50 years and older with the CC genotype demonstrated improved disease-free survival as compared to patients with CT and TT genotypes. The G2677A/T SNP showed a non-significant trend toward an increased risk of progression in Cox regression analysis. The C1236T variant displayed no clear evidence of effect. There was no association with outcome to haplotype analysis. These findings suggest that ABCB1 SNPs, specifically C3435T , may play a role in diminishing treatment efficacy of doxorubicin, particularly among older patients. Given the modest sample size, the absence of multiplicity adjustment in primary tests, and the lack of an independent validation cohort, these results should be regarded as exploratory and hypothesis-generating. They provide population-specific characterization for an under-studied Middle-Eastern population and require confirmation in larger, independent cohorts before any clinical application can be considered.