Novillo Apolonia, Gaibar María, Romero-Lorca Alicia, Malón Diego, Antón Beatriz, Moreno Amalia, Fernández-Santander Ana
Medicine Faculty, Cellular Biology Section Department, Complutense University, 28040 Madrid, Spain.
Human Genetic Variability Group, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid-Getafe University Hospital-Universidad Europea de Madrid), 28046 Madrid, Spain.
Cancers (Basel). 2023 Jan 26;15(3):763. doi: 10.3390/cancers15030763.
The addition to chemotherapy of anti-HER2 drugs such as trastuzumab or pertuzumab has improved outcomes in HER2-positive breast cancer patients. However, resistance to these drugs in some patients remains a major concern. This study examines the possible association between the response to neoadjuvant anti-HER2 treatment in breast cancer patients and the presence of 28 SNPs in 17 genes involved in different cell processes (, , , , , , , , , , chr6 intergenic region, , , , , , and ). Tumor samples from 50 women with early breast cancer were genotyped using the iPlexGold chemistry and MassARRAY platform, and patients were classified as good responders (Miller-Payne tumor grades 4-5) and poor responders (Miller-Payne tumor grades 1-3), as assessed upon surgery after 6 months of treatment. Proportions of patients with the (rs1058808) SNP double mutation were higher in good (58.62%) than poor (20%) responders ( = 0.025). Similarly, proportions of patients carrying the synonymous SNP rs2070096 () (wv + vv) were higher in patients showing a pathological complete response (46.67%) than in those not showing this response (15.15%) ( = 0.031). The SNPs rs1058808 () and rs2070096 () were identified here as potential biomarkers of a good response to anti-HER2 treatment.
在化疗中添加曲妥珠单抗或帕妥珠单抗等抗HER2药物可改善HER2阳性乳腺癌患者的治疗效果。然而，部分患者对这些药物产生耐药性仍是一个主要问题。本研究调查了乳腺癌患者对新辅助抗HER2治疗的反应与17个参与不同细胞过程的基因（、、、、、、、、、、6号染色体基因间区域、、、、、、和）中28个单核苷酸多态性（SNP）之间的可能关联。采用iPlexGold化学法和MassARRAY平台对50例早期乳腺癌女性患者的肿瘤样本进行基因分型，并根据治疗6个月后手术时的评估，将患者分为反应良好者（米勒-佩恩肿瘤分级4 - 5级）和反应不佳者（米勒-佩恩肿瘤分级1 - 3级）。反应良好者（58.62%）中携带（rs1058808）SNP双突变的患者比例高于反应不佳者（20%）（P = 0.025）。同样，病理完全缓解的患者（46.67%）中携带同义SNP rs2070096（）（wv + vv）的患者比例高于未出现此反应的患者（15.15%）（P = 0.031）。在此，SNP rs1058808（）和rs2070096（）被确定为抗HER2治疗反应良好的潜在生物标志物。
