ABCB1 polymorphism as a prognostic factor in breast cancer patients with neoadjuvant chemotherapy.

Authors

null

Hee Jun Kim

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

Organizations

Chung-Ang University Hospital, Seoul, South Korea, Department of Internal Medicine and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea, Seoul National University, College of Medicine, Seoul, South Korea, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea, Cancer Research Institute and Department of Surgery, Seoul National University, College of Medicine, Seoul, South Korea, Department of Clinical Pharmacology, Seoul National University Hospital, Seoul, South Korea, Department of Pathology, Seoul National University College of Medicine, Seoul University Hospital, Seoul, South Korea, Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea

Research Funding

No funding sources reported

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 Details

Meeting

2014 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer - Triple-Negative/Cytotoxics/Local Therapy

Track

Breast Cancer

Sub Track

Cytotoxic Chemotherapy

Citation

J Clin Oncol 32:5s, 2014 (suppl; abstr 1038)

DOI

10.1200/jco.2014.32.15_suppl.1038

Abstract #

1038

Poster Bd #

131

Abstract Disclosures