1. Association of plasma docetaxel levels with ABCB1 gene polymorphisms and tumour response in locally advanced breast cancer patients of South India on neo‐adjuvant chemotherapy
- Author
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Gerard Marshall Raj, Rekha Priyadarshini, Rajan Sundaram, Ananthakrishnan Ramesh, Smita Kayal, and Deepak Gopal Shewade
- Subjects
Adult ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,ATP Binding Cassette Transporter, Subfamily B ,Genotype ,medicine.medical_treatment ,India ,Antineoplastic Agents ,Breast Neoplasms ,Single-nucleotide polymorphism ,Docetaxel ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Tandem Mass Spectrometry ,Internal medicine ,medicine ,Humans ,SNP ,Pharmacology (medical) ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Genotyping ,Aged ,Chemotherapy ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Neoadjuvant Therapy ,SNP genotyping ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,business ,Chromatography, Liquid ,medicine.drug - Abstract
Genetic factors could be attributed to the variability in docetaxel plasma levels and its subsequent therapeutic response. The objectives of this study were to assess the effect of ABCB1 gene polymorphisms [SNPs rs1045642 (C3435T) and rs1128503 (C1236T)] on docetaxel plasma levels and also to analyze the influence of docetaxel plasma levels on tumour response in the ethnically distinct South Indian population. 104 locally advanced breast cancer (LABC) patients on docetaxel-based neo‐adjuvant chemotherapy (NACT) were included. The plasma docetaxel levels were estimated using the validated reverse phase liquid chromatography with mass spectrometry (LC–MS/MS). DNA was extracted (phenol‐chloroform extraction method) and the real‐time PCR system using validated TaqMan® SNP genotyping assay method was used for genotyping. Tumour response was assessed by RECIST criteria based on the MRI images. Patients with “CT/TT” genotype of the SNP C1236T had a C0/Ct ratio of 1.6 times higher than those with “CC” genotype (13.5 ± 6.5 vs 8.3 ± 3.1, p = 0.002). Though not significant, patients with “CT/TT” genotype had greater initial plasma concentration (C0) and area under the plasma concentration–time curve (AUC0−t). Conversely, the SNP C3435T was not associated with the plasma docetaxel levels. Furthermore, the C0 and normalized C0 were found to be higher in tumour responders compared to non-responders (p
- Published
- 2020
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