Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000 Guizhou, China.
Department of Hygiene Toxicology, School of Public Health, Zunyi Medical University, Zunyi, 563000 Guizhou, China.
Biomed Res Int. 2019 Feb 6;2019:7073498. doi: 10.1155/2019/7073498. eCollection 2019.
The expression of the transcription factor FOXA1 is associated with the prognosis of estrogen receptor (ER)-positive breast cancer, and the genetic variant rs4442975 can affect FOXA1 function. Therefore, we investigated the association between rs4442975 and the efficacy of neoadjuvant chemotherapy for luminal A type breast cancer and evaluated its toxic side effects in a Chinese population. One hundred seventy-five patients with luminal A type breast cancer receiving neoadjuvant chemotherapy with a combination protocol of epirubicin and docetaxel (ET protocol) were enrolled in the study. Genotyping was performed in a randomized manner to identify candidate genetic variants. Unconditional logistic regression analysis was used to analyze the association of the variant with the efficacy and side effects of neoadjuvant chemotherapy. The results did not reveal any positive association with the efficacy of neoadjuvant chemotherapy, with an odds ratio (OR) of 0.73 (95% confidence interval = 0.27-1.94) in the additive model. However, analysis of the toxic side effects of neoadjuvant chemotherapy showed that rs4442975 was associated with bone marrow suppression, with an OR of 0.38 (95% confidence interval = 0.17-0.73, = 0.005) in the dominant model. In summary, the functional genetic variant rs4442975 was associated with bone marrow suppression during neoadjuvant chemotherapy for luminal A type breast cancer. These results may help establish reliable molecular markers for predicting the prognosis of personalized treatment for luminal A type breast cancer and thereby contribute to the development of appropriate therapies.
转录因子 FOXA1 的表达与雌激素受体 (ER) 阳性乳腺癌的预后相关，而遗传变异 rs4442975 可以影响 FOXA1 的功能。因此，我们研究了 rs4442975 与 luminal A 型乳腺癌新辅助化疗疗效的关系，并在中国人群中评估了其毒性副作用。本研究纳入了 175 例接受表柔比星联合多西他赛新辅助化疗 (ET 方案) 的 luminal A 型乳腺癌患者。采用随机分组的方法进行基因分型，以鉴定候选遗传变异。采用条件逻辑回归分析来分析该变异与新辅助化疗疗效和副作用的关系。结果未发现该变异与新辅助化疗疗效有任何正相关，加性模型中的比值比 (OR) 为 0.73 (95%置信区间 = 0.27-1.94)。然而，新辅助化疗毒性副作用的分析表明，rs4442975 与骨髓抑制相关，显性模型中的 OR 为 0.38 (95%置信区间 = 0.17-0.73， = 0.005)。总之，功能遗传变异 rs4442975 与 luminal A 型乳腺癌新辅助化疗期间的骨髓抑制有关。这些结果可能有助于建立可靠的分子标志物，预测 luminal A 型乳腺癌个体化治疗的预后，从而为制定适当的治疗方案做出贡献。
