ABCB1 polymorphism as prognostic factor in breast cancer patients treated with docetaxel and doxorubicin neoadjuvant chemotherapy

• Published in: Cancer science Vol. 106; no. 1; pp. 86 - 93
• Main Authors: Kim, Hee‐Jun, Im, Seock‐Ah, Keam, Bhumsuk, Ham, Hye Seon, Lee, Kyung Hun, Kim, Tae Yong, Kim, Yu Jung, Oh, Do‐Youn, Kim, Jee Hyun, Han, Wonshik, Jang, In‐Jin, Kim, Tae‐You, Park, In Ae, Noh, Dong Young
• Format: Journal Article
• Language: English
• Published: England BlackWell Publishing Ltd 01.01.2015
• Subjects: ABCB1 Gene; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; ATP Binding Cassette Transporter, Sub-Family B - genetics; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - mortality; C3435T; Carcinoma, Ductal, Breast - drug therapy; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - mortality; Chemotherapy, Adjuvant; Cytochrome P-450 CYP3A - genetics; Doxorubicin - administration & dosage; Female; Gene Frequency; Genetic Association Studies; Humans; Kaplan-Meier Estimate; Middle Aged; Multivariate Analysis; neoadjuvant chemotherapy; Neoadjuvant Therapy; Original; Polymorphism, Single Nucleotide; Prognosis; Proportional Hazards Models; single nucleotide polymorphism; Taxoids - administration & dosage; neoadjuvant chemotherapy; breast cancer; ABCB1 Gene; C3435T; single nucleotide polymorphism
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.12560

Expression of the adenosine triphosphate‐binding cassette B1 (ABCB1) transporter and P‐glycoprotein are associated with resistance to anticancer drugs. The purpose of this study was to investigate the role of single nucleotide polymorphism in the ABCB1 and CYP3A genes in breast cancer patients who were treated with neoadjuvant chemotherapy. Stage II/III breast cancer patients were treated with three cycles of neoadjuvant, after which the patients received curative surgery and adjuvant chemotherapy. The polymorphisms of ABCB1 and CYP3A were genotyped. The correlation of polymorphism of ABCB1, CYP3A, and clinical outcomes was analyzed. Among the 216 patients, ABCB1 3435TT genotype had a longer overall survival (OS). than CC/CT. Multivariate analyses demonstrated that good PS, invasive ductal carcinoma, non‐triple negative phenotype and initial operable stage were significantly associated with a lower death risk. ABCB1 3435TT genotype had a higher AUC than CC/CT for docetaxel. These higher AUCs in the C3435TT was associated with increased toxicities of neutropenia and diarrhea. 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. This study results provides valuable information on individualized therapy according to genotypes. ABCB1 encodes P‐glycoproteins (P‐gp), a membrane‐bound efflux pump, which has been shown to remove chemotherapeutic drugs including docetaxel and doxorubicin from the cells. In this prospective observational study, ABCB1 C3435T polymorphism was significantly associated with improved survival as well as increased frequency of toxicity after neoadjuvant combination chemotherapy of docetaxel and doxorubicin in Asian patients with stage II or III breast cancer. This study results provides valuable information on individualized therapy in selecting optimal patients and drugs according to genotypes.