Chung-Ang University Hospital, Seoul, South Korea
Hee Jun Kim , Seock-Ah Im , Hye Seon Ham , Kyung Hun Lee , Tae Yong Kim , Yu Jeong Kim , Do-Youn Oh , Jee Hyun Kim , Wonshik Han , In-Jin Jang , Tae-You Kim , In Ae Park , Dong Young Noh
Background: Expression of the adenosine triphosphate-binding cassette B1(ABCB1) transporter and P-glycoprotein are associated with resistance to anticancer drugs. The purpose of this thesis was to investigate the role of single nucleotide polymorphism (SNP) in the ABCB1 and CYP3A genes in breast cancer patients who were treated with neoadjuvant docetaxel and doxorubicin chemotherapy. Methods: Stage II or III breast cancer patients were treated with 3 cycles of neoadjuvant, after which the patients received curative surgery and adjuvant chemotherapy with the same regimen. The polymorphisms of ABCB1 (C3435T, G2677T/A, and C1236T) and CYP3A were genotyped. The correlation of genetic polymorphisms of ABCB1, CYP3A, and clinical outcomes was analyzed. Results: Among the 216 patients, ABCB1 3435TT genotype had a longer OS than CT/TT. With univariate analysis, good PS, invasive ductal carcinoma, initial operable stage, ER-positivity, non-triple negative phenotype, breast conserving surgery and the TT genotype of C3435T were associated with a lower risk of death. Multivariate analyses demonstrated that good PS, invasive ductal carcinoma, non-triple negative phenotype and initial operable stage were significantly associated with the OS. ABCB1 3435TT genotype had a higher AUC than CC/CT genotype for docetaxel (p=0.031). These higher AUCs in the C3435TT genotype was associated with increased toxicities of neutropenia (p=0.037) and diarrhea (p=0.017). Conclusions: This study showed that the genetic polymorphism of ABCB1 C3435T might be associated with a longer OS. Our results also suggest that the prediction of docetaxel toxicity might be possible for C3435T polymorphism. Larger prospective studies as well as functional studies in human subjects are warranted.
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Abstract Disclosures
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