Clinical utility of ABCB1 and ABCG2 genotyping for assessing the clinical and pathological response to FAC therapy in Mexican breast cancer patients
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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 %2b 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. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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ABCB1; ABCG2; Clinical response; FAC chemotherapy; Pathological response; Polymorphisms breast cancer resistance protein; cyclophosphamide; doxorubicin; fluorouracil; genomic DNA; multidrug resistance protein 1; ABCB1 protein, human; ABCG2 protein, human; antineoplastic agent; cyclophosphamide; doxorubicin; fluorouracil; tumor protein; adult; anemia; Article; blood toxicity; breast cancer; breast carcinoma; breast carcinoma in situ; cancer combination chemotherapy; cancer patient; cancer prognosis; cancer resistance; chemosensitivity; chemotherapy induced emesis; chemotherapy induced nausea; controlled study; diarrhea; estrogen receptor negative breast cancer; estrogen receptor positive breast cancer; family history; female; genotype; hand foot syndrome; histopathology; human; human epidermal growth factor receptor 2 negative breast cancer; human epidermal growth factor receptor 2 positive breast cancer; intraductal carcinoma; invasive carcinoma; leukopenia; lobular carcinoma; luminal A breast cancer; luminal B breast cancer; major clinical study; menarche; Mexican; middle aged; neoadjuvant chemotherapy; observational study; priority journal; progesterone receptor negative breast cancer; progesterone receptor positive breast cancer; real time polymerase chain reaction; response evaluation criteria in solid tumors; retrospective study; single nucleotide polymorphism; thrombocytopenia; treatment response; triple negative breast cancer; breast tumor; genetics; genotype; neoadjuvant therapy; procedures; Antineoplastic Combined Chemotherapy Protocols; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Genotype; Humans; Middle Aged; Neoadjuvant Therapy; Neoplasm Proteins; Polymorphism, Single Nucleotide; Retrospective Studies
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