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.
Oncología Ginecológica, Hospital Central "Dr. Ignacio Morones Prieto", San Luis Potosí, SLP, Mexico.
Cancer Chemother Pharmacol. 2021 Jun;87(6):843-853. doi: 10.1007/s00280-021-04244-y. Epub 2021 Mar 19.
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.
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).
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.
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.
在一些局部晚期乳腺癌患者中，对氟尿嘧啶、多柔比星和环磷酰胺（FAC）新辅助化疗的耐药性仍然是一线治疗的主要障碍之一。我们研究了 FAC 新辅助化疗在墨西哥乳腺癌女性患者中的临床和病理反应及其与 ABC 转运体中存在的 SNP 的可能关联，这些 SNP 可作为预测化疗耐药性的标志物。
共纳入 102 例接受 FAC 新辅助化疗的患者进行研究。通过从基因组 DNA 进行 RT-PCR 进行 SNP 分析。分析了两个 SNP：ABCB1 rs1045642（3435 C > T）和 ABCG2 rs2231142（421 G > T）。
在临床反应评估中，ABCB1 C3435T 基因型与乳腺癌化疗耐药和化疗敏感患者之间存在显著关联（p < 0.05）。在早期临床反应中，与基因型 T/T 相比，基因型 C/C 或 C/T 的患者更有可能对新辅助治疗敏感（OR = 4.055；p = 0.0064）。ABCB1 基因多态性与 FAC 化疗病理反应之间的关联分析表明，C/C + C/T 基因型是对化疗耐药的保护因素（OR = 3.714；p = 0.0104）。ABCG2 多态性与 FAC 新辅助化疗的临床或病理反应率无相关性（p = 0.2586）。
早期临床反应及其与 ABCB1 转运体中的 SNP 的关联可保留至新辅助化疗的病理反应；因此，它可用作预测墨西哥人群局部晚期乳腺癌患者化疗耐药性的标志物。
