Eneida Turiján-Espinoza1, Víctor Manuel Ruíz-Rodríguez1, Edith Elena Uresti-Rivera1, Ernesto Martínez-Leija1, José de Jesús Zermeño-Nava2, Arturo Guel-Pañola3, Silvia Romano-Moreno4, Juan Manuel Vargas-Morales5, Diana Patricia Portales-Pérez6. 1. Translational and Molecular Medicine Department, Faculty of Chemical Sciences, Research Center for Health Sciences and Biomedicine (CICSaB), Autonomous University of San Luis Potosí, UASLP, San Luis Potosí, SLP, Mexico. 2. Oncología Ginecológica, Hospital Central "Dr. Ignacio Morones Prieto", San Luis Potosí, SLP, Mexico. 3. Oncología Adultos, Hospital Central "Dr. Ignacio Morones Prieto", San Luis Potosí, SLP, Mexico. 4. Laboratory of Pharmacy, Faculty of Chemical Sciences, Autonomous University of San Luis Potosí, San Luis Potosí, SLP, Mexico. 5. Laboratory of Clinical Analyses, Faculty of Chemical Sciences, Autonomous University of San Luis Potosí, San Luis Potosí, SLP, Mexico. 6. Translational and Molecular Medicine Department, Faculty of Chemical Sciences, Research Center for Health Sciences and Biomedicine (CICSaB), Autonomous University of San Luis Potosí, UASLP, San Luis Potosí, SLP, Mexico. dportale@uaslp.mx.
Abstract
PURPOSE: Resistance to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) in some patients with locally advanced breast cancer remains one of the main obstacles to first-line treatment. We investigated clinical and pathological responses to FAC neoadjuvant chemotherapy in Mexican women with breast cancer and their possible association with SNPs present in ABC transporters as predictors of chemoresistance. MATERIALS: A total of 102 patients undergoing FAC neoadjuvant chemotherapy were included in the study. SNP analysis was performed by RT-PCR from genomic DNA. Two SNPs were analyzed: ABCB1 rs1045642 (3435 C > T) and ABCG2 rs2231142 (421 G > T). RESULTS: In clinical response evaluation, significant associations were found between the ABCB1 C3435T genotype and breast cancer chemoresistant and chemosensitive patients (p < 0.05). In the early clinical response, patients with genotype C/C or C/T were more likely to be chemosensitive to neoadjuvant therapy than patients with genotype T/T (OR = 4.055; p = 0.0064). Association analysis between the ABCB1 gene polymorphism and the pathologic response to FAC chemotherapy showed that the C/C + C/T genotype was a protective factor against chemoresistance (OR = 3.714; p = 0.0104). Polymorphisms in ABCG2 indicated a lack of association with resistance to chemotherapy (p = 0.2586) evaluating the clinical or pathological response rate to FAC neoadjuvant chemotherapy. CONCLUSION: The early clinical response and its association with SNPs in the ABCB1 transporter are preserved until the pathological response to neoadjuvant chemotherapy; therefore, it could be used as a predictor of chemoresistance in locally advanced breast cancer patients of the Mexican population.
PURPOSE: Resistance to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) in some patients with locally advanced breast cancer remains one of the main obstacles to first-line treatment. We investigated clinical and pathological responses to FAC neoadjuvant chemotherapy in Mexican women with breast cancer and their possible association with SNPs present in ABC transporters as predictors of chemoresistance. MATERIALS: A total of 102 patients undergoing FAC neoadjuvant chemotherapy were included in the study. SNP analysis was performed by RT-PCR from genomic DNA. Two SNPs were analyzed: ABCB1 rs1045642 (3435 C > T) and ABCG2 rs2231142 (421 G > T). RESULTS: In clinical response evaluation, significant associations were found between the ABCB1C3435T genotype and breast cancer chemoresistant and chemosensitive patients (p < 0.05). In the early clinical response, patients with genotype C/C or C/T were more likely to be chemosensitive to neoadjuvant therapy than patients with genotype T/T (OR = 4.055; p = 0.0064). Association analysis between the ABCB1 gene polymorphism and the pathologic response to FAC chemotherapy showed that the C/C + C/T genotype was a protective factor against chemoresistance (OR = 3.714; p = 0.0104). Polymorphisms in ABCG2 indicated a lack of association with resistance to chemotherapy (p = 0.2586) evaluating the clinical or pathological response rate to FAC neoadjuvant chemotherapy. CONCLUSION: The early clinical response and its association with SNPs in the ABCB1 transporter are preserved until the pathological response to neoadjuvant chemotherapy; therefore, it could be used as a predictor of chemoresistance in locally advanced breast cancerpatients of the Mexican population.
Entities:
Keywords:
ABCB1; ABCG2; Clinical response; FAC chemotherapy; Pathological response; Polymorphisms
Authors: T Byrski; T Huzarski; R Dent; J Gronwald; D Zuziak; C Cybulski; J Kladny; B Gorski; J Lubinski; S A Narod Journal: Breast Cancer Res Treat Date: 2008-07-23 Impact factor: 4.872