PD-1抑制剂在三阴性乳腺癌新辅助治疗中的疗效及影响因素
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PD-1 inhibitors in neoadjuvant therapy for triple-negative breast cancer: efficacy and influencing factors
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    摘要:

    目的 探讨程序性死亡蛋白1(PD-1)抑制剂在三阴性乳腺癌(TNBC)新辅助治疗中的疗效及其相关影响因素。方法 纳入2018年1月1日至2024年1月1日在中国人民解放军总医院第五医学中心接受新辅助治疗、符合入组要求的TNBC患者86例,收集其临床病理资料。按照新辅助治疗方案分为两组,40例接受TP+PD-1抑制剂(紫杉醇+卡铂+帕博利珠单抗)方案治疗的患者归入TP+PD-1抑制剂组,46例接受TP(紫杉醇+卡铂)方案治疗的患者归入TP组,比较两组患者新辅助治疗6周期后的疗效及不良反应发生率的差异。根据新辅助治疗疗效,将患者分为病理完全缓解(pCR)组和非pCR组,采用多因素logistic逐步回归分析探讨新辅助治疗疗效的独立影响因素。随访至2024年12月31日,采用Kaplan-Meier法进行生存分析。结果 TP+PD-1抑制剂组与TP组患者新辅助治疗后客观缓解率差异无统计学意义[95.0%(38/40) vs 91.3%(42/46),P=0.351],TP+PD-1抑制剂组pCR率高于TP组[65.0%(26/40) vs 43.5%(20/46),P=0.047]。两组的无病生存期、总生存期及不良反应发生率差异均无统计学意义(均P>0.05)。多因素logistic逐步回归分析发现,Ki-67表达、治疗方案是新辅助治疗后pCR的影响因素(OR=3.382,95%CI 1.290~8.868,P=0.013;OR=2.524,95%CI 1.013~6.285,P=0.047)。pCR组出现远处转移并死亡1例,非pCR组出现远处转移8例、死亡4例。pCR组无病生存期长于非pCR组(P=0.031),但总生存期与pCR组相比差异无统计学意义(P=0.087)。结论 与6周期TP方案相比,6周期TP+PD-1抑制剂方案能够提高TNBC患者新辅助治疗的pCR率,且不良反应可控,可作为TNBC新辅助治疗的优选方案。Ki-67可作为pCR的预测指标。获得pCR的TNBC患者无病生存期优于未获得pCR的患者。

    Abstract:

    Objective To investigate the efficacy and influencing factors of programmed death-1 (PD-1) inhibitors in neoadjuvant chemotherapy for triple-negative breast cancer (TNBC). Methods A total of 86 patients with TNBC who received neoadjuvant therapy in The Fifth Medical Center, PLA General Hospital between Jan. 1, 2018, and Jan. 1, 2024 and met the inclusion criteria were enrolled, and their clinicopathological data were collected. Based on the neoadjuvant treatment regimens, 40 patients who received TP+PD-1 inhibitor (paclitaxel+carboplatin+pembrolizumab) were assigned to TP+PD-1 inhibitor group, and 46 patients who received TP (paclitaxel+carboplatin) were assigned to TP group. The efficacy and incidence of adverse events were compared between the 2 groups after 6 cycles of neoadjuvant therapy. According to the efficacy of neoadjuvant therapy, the patients were further categorized into pathological complete response (pCR) group and non-pCR group. Multivariate logistic stepwise regression analysis was performed to identify independent factors influencing neoadjuvant treatment efficacy. Patients were followed up until Dec. 31, 2024, and survival analysis was conducted using Kaplan-Meier method. Results There was no significant difference in the objective response rates between the TP+PD-1 inhibitor group and TP group after neoadjuvant therapy (95.0% [38/40] vs 91.3% [42/46], P=0.351]. However, the pCR rate was significantly higher in the TP+PD-1 inhibitor group compared with the TP group (65.0% [26/40] vs 43.5% [20/46], P=0.047). There were no significant differences between the 2 groups in terms of disease-free survival, overall survival, or incidence of adverse events (all P>0.05). Multivariate logistic stepwise regression analysis revealed that the expression of Ki-67 and treatment regimen were influencing factors of pCR after neoadjuvant therapy (odds ratio [OR]=3.382, 95% confidence interval [95%CI] 1.290-8.868, P=0.013; OR=2.524, 95%CI 1.013-6.285, P=0.047). One case of distant metastasis and death occurred in the pCR group, while 8 cases of distant metastasis and 4 deaths occurred in the non-pCR group. The disease-free survival was significantly longer in the pCR group than in the non-pCR group (P=0.031), while the overall survival was similar between the 2 groups (P=0.087). Conclusion Compared with the 6-cycle TP regimen, the 6-cycle TP combined with PD-1 inhibitor regimen can improve the pCR rate in the neoadjuvant treatment of TNBC, with manageable adverse events, suggesting it may serve as a preferred option for TNBC neoadjuvant therapy. Ki-67 expression may serve as a predictive biomarker for achieving pCR. TNBC patients who achieved pCR have better disease-free survival than those who did not.

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  • 收稿日期:2025-03-10
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  • 在线发布日期: 2025-09-22
  • 出版日期: 2025-09-20
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