三阴性乳腺癌新辅助化疗的预后及与血清维生素D水平和Ki-67、PD-L1表达情况的相关性

Prognosis after neoadjuvant chemotherapy and its correlation with serum vitamin D level and expression of Ki-67 and PD-L1 in patients with triple negative breast cancer

目的探讨三阴性乳腺癌(TNBC)患者新辅助化疗后的预后情况及与血清维生素D水平和肿瘤组织中Ki-67、程序性死亡受体配体1(PD-L1)表达情况的相关性。方法选择58例TNBC患者,所有患者均在术前接受4~6个周期的新辅助化疗,并在完成新辅助化疗后的2~3周进行手术治疗。术后对患者进行随访,观察患者的复发转移情况、无进展生存时间及总生存时间。应用酶联免疫吸附试验检测患者术后的血清维生素D水平,应用免疫组织化学法检测肿瘤组织中Ki-67、PD-L1的表达水平,采用Spearman法分析上述指标与患者预后的相关性。结果58例TNBC患者经新辅助化疗及手术治疗,病理检查结果显示,19例患者完全缓解,39例患者具有残留癌。所有患者均完成随访,随访时间为9~30个月,中位随访时间为20个月;随访期间3例患者出现复发转移,4例患者因乳腺癌死亡。58例TNBC患者术后的血清维生素D水平为(17.12±1.21)μg/L。完全缓解患者的血清维生素D水平明显高于残留癌患者(P﹤0.01),完全缓解患者肿瘤组织中Ki-67的高表达率低于残留癌患者(P﹤0.05);完全缓解和残留癌患者肿瘤组织中PD-L1的阳性表达率比较,差异无统计学差异(P﹥0.05)。相关性分析结果显示,血清维生素D水平与TNBC患者的无进展生存时间呈正相关(r=0.756,P﹤0.05),而肿瘤组织中Ki-67高表达和PD-L1阳性表达均与TNBC患者的总生存时间和无进展生存时间无相关性(P﹥0.05)。结论维生素D是反映TNBC患者预后的重要指标,肿瘤组织中Ki-67的表达情况可在一定程度上反映TNBC的治疗效果。

Objective To investigate the prognosis of patients with triple negative breast cancer(TNBC) after neoadjuvant chemotherapy and to analyze its correlation with serum vitamin D level and expression of Ki-67 and programmed cell death 1 ligand 1(PD-L1) in tumor tissues. Method A total of 58 patients with TNBC, who were assigned to receive 4 to 6 cycles of neoadjuvant chemotherapy prior to surgery and have time interval between neoadjuvant chemotherapy and surgery up to 2 to 3 weeks, were enrolled. The patients were followed up after surgery to observe recurrence and metastasis, progression-free survival and overall survival. Serum vitamin D level after chemotherapy were measured by enzyme-linked immunosorbent assay(ELISA) and the expression of Ki-67 and PD-L1 in tumor tissues were detected by immunohistochemistry. The correlation between the indicators above and the prognosis of patients using Spearman correlation analysis. Result 58 patients with TNBC had underwent surgery combined with neoadjuvant chemotherapy. Among them, 19 patients showed pathological complete response and 39 patients were found to have residual cancer according to the pathological examination. All patients completed the follow-up and the duration of follow-up was 9 to 30 months,with a median follow-up of 20 months. During this period, 3 patients were reported with recurrence or metastasis, and 4 patients died due to breast cancer. The average serum vitamin D level of the 58 patients was(17.12±1.21) μg/L, and the serum vitamin D level of patients with complete response was significant higher than that of patients with residual cancer(P<0.01). The high expression rate of Ki-67 in patients with complete response was significant lower than that of patients with residual cancer(P<0.05);the positive expression rate of PD-L1 in patients with complete response was not statistically different from that in patients with residual cancer(P>0.05). Correlation analysis showed a significant positive correlation between serum vitamin D level and progression-free survival of patients with TNBC(r=0.756, P<0.05);the high expression of Ki-67 and the positive expression of PD-L1 in tumor tissues were not associated with the overall survival and progression-free survival of patients with TNBC(P>0.05). Conclusion Vitamin D plays an important role in indicating the prognosis of patients with TNBC. The expression of Ki-67 in tumor tissues reflects the therapeutic efficacy of the treatment for TNBC to some extent.