Miyagawa Yoshimasa, Yanai Ayako, Yanagawa Takehiro, Inatome Junichi, Egawa Chiyomi, Nishimukai Arisa, Takamoto Kaori, Morimoto Takashi, Kikawa Yuichiro, Suwa Hirofumi, Taji Tomoe, Yamaguchi Ai, Okada Yuki, Sata Atsushi, Fukui Reiko, Bun Ayako, Ozawa Hiromi, Higuchi Tomoko, Fujimoto Yukie, Imamura Michiko, Miyoshi Yasuo
Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo 660-8511, Japan.
Oncotarget. 2020 Jan 7;11(1):86-98. doi: 10.18632/oncotarget.27423.
The effect of bevacizumab plus paclitaxel therapy on progression-free survival (PFS) is prominent; however, no overall survival (OS) benefit has been demonstrated. Our aim was to study the predictive efficacy of peripheral immune-related parameters, neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and c-reactive protein (CRP) in locally advanced and metastatic breast cancers. A total of 179 patients treated with bevacizumab plus paclitaxel were recruited from three institutes in the test cohort. The cut-off values of NLR, ALC, and CRP were set at 3, 1500/μL, and 1.0 mg/dL, respectively, and baseline values of these factors were measured. The PFS of patients with NLR-low was significantly longer than that of patients with -high (median, 12.6 vs. 7.2 months; hazard ratio (HR), 0.48, 95% confidence interval (95% CI), 0.31-0.73; = 0.0004). OS of patients with NLR-low was significantly better than those with-high (22.2 vs. 13.5 months; HR, 0.57, 95% CI, 0.39-0.83; = 0.0032). Similarly, improved PFS and OS were recognized in patients with CRP-low as compared with patients with -high (HR, 0.44, 95% CI, 0.28-0.68; = 0.0001 and HR, 0.39, 95% CI, 0.26-0.61, < 0.0001, respectively). In the validation cohort from two institutes ( = 57), similar significant improvements in PFS and OS were confirmed for patients with NLR-low ( = 0.0344 and = 0.0233, respectively) and CRP-low groups ( < 0.0001 and = 0.0001, respectively). Low levels of NLR and CRP at baseline were significantly associated with improved prognosis in patients treated with bevacizumab plus paclitaxel.
贝伐单抗联合紫杉醇治疗对无进展生存期（PFS）的影响显著；然而，尚未证实其对总生存期（OS）有获益。我们的目的是研究外周免疫相关参数，即中性粒细胞与淋巴细胞比值（NLR）、绝对淋巴细胞计数（ALC）和C反应蛋白（CRP）在局部晚期和转移性乳腺癌中的预测效力。从测试队列中的三个机构招募了总共179例接受贝伐单抗联合紫杉醇治疗的患者。将NLR、ALC和CRP的临界值分别设定为3、1500/μL和1.0mg/dL，并测量这些因素的基线值。NLR低的患者的PFS明显长于NLR高的患者（中位数，12.6个月对7.2个月；风险比（HR），0.48，95%置信区间（95%CI），0.31 - 0.73；P = 0.0004）。NLR低的患者的OS明显优于NLR高的患者（22.2个月对13.5个月；HR，0.57，95%CI，0.39 - 0.83；P = 0.0032）。同样，与CRP高的患者相比，CRP低的患者的PFS和OS得到改善（HR，0.44，95%CI，0.28 - 0.68；P = 0.0001和HR，0.39，95%CI，0.26 - 0.61，P均<0.0001）。在来自两个机构的验证队列（n = 57）中，对于NLR低的患者（PFS，P = 0.0344；OS，P = 0.0233）和CRP低的组（PFS，P < 0.0001；OS，P = 0.0001），PFS和OS的类似显著改善得到证实。基线时NLR和CRP水平低与接受贝伐单抗联合紫杉醇治疗的患者预后改善显著相关。
