Influence of ABCB1 Polymorphisms on Outcomes of Breast Cancer

Abstract

Background: The importance of genotyping ABCB1 polymorphism genes in predicting the outcome of breast cancer patients receiving anthracycline and taxane-based regimens was reported. However, interethnic variations play a significant role in predicting the response to chemotherapy.Materials and Methods: This prospective study was carried out to assess the influence of ABCB1 genotypes on breast cancer response. Genotyping of ABCB1 was carried out by real-time PCR (7300 Applied Biosystems; Life Technologies Corporation, USA) using TaqMan SNP genotyping assays, Response assessments were evaluated as per RECIST criteria version.Results: A total of 170 locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy were recruited. The genotype frequencies of ABCB11236 homozygous wild-type variant CC, the heterozygous variant CT, and the mutant homozygous variant TT were 23.0%, 44.0%, and 33.0% respectively. The genotype frequencies of ABCB1 1236 homozygous wild-type variant CC, the heterozygous variant CT, and the mutant homozygous variant TT were 28.0%, 42.0%, and 30.0% respectively. Similarly, the ABCB1 2677 wild-type variant GG (18%), TT (26% AA (2% the heterozygous variant GA (7%), GT (45%), TA (2%), and the mutant homozygous variant were observed.Conclusion: Our study revealed that ABCB1 3435 C>T polymorphism was associated with response as patients with ABCB1 3435 mutant genotypes had better response. Patients having ABCB1 1236 mutant genotypes (CT & TT) had more risk for neutropenia and vomiting, suggesting the significance of ABCB1 genotypes in predicting response and toxicity in anthracycline-based regimens.

Keywords: Breast cancer; ABCB1; Clinical response; Neutropenia; Multidrug-resistant protein Efflux transporter