Baseline neutrophil-to-lymphocyte ratio and c-reactive protein predict efficacy of treatment with bevacizumab plus paclitaxel for locally advanced or metastatic breast cancer

// Yoshimasa Miyagawa 1 , Ayako Yanai 2 , Takehiro Yanagawa 2 , Junichi Inatome 2 , Chiyomi Egawa 2 , Arisa Nishimukai 3 , Kaori Takamoto 3 , Takashi Morimoto 3 , Yuichiro Kikawa 4 , Hirofumi Suwa 5 , Tomoe Taji 5 , Ai Yamaguchi 5 , Yuki Okada 5 , Atsushi Sata 1 , Reiko Fukui 1 , Ayako Bun 1 , Hiromi Ozawa 1 , Tomoko Higuchi 1 , Yukie Fujimoto 1 , Michiko Imamura 1 and Yasuo Miyoshi 1 1 Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan 2 Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo 660-8511, Japan 3 Department of Breast Surgery, Yao Municipal Hospital, Yao, Osaka 581-0069, Japan 4 Department of Breast Surgery, Kobe City Medical Center General Hospital, Chuo-ku, Kobe, Hyogo 650-0047, Japan 5 Department of Breast Surgery, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Hyogo 660-8550, Japan Correspondence to: Yasuo Miyoshi, email: ymiyoshi@hyo-med.ac.jp Keywords: breast cancer; bevacizumab; neutrophil-to-lymphocyte ratio; c-reactive protein; predictive marker Received: August 19, 2019     Accepted: December 21, 2019     Published: January 07, 2020 ABSTRACT 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; p = 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; p = 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; p = 0.0001 and HR, 0.39, 95% CI, 0.26–0.61, p < 0.0001, respectively). In the validation cohort from two institutes ( n = 57), similar significant improvements in PFS and OS were confirmed for patients with NLR-low ( p = 0.0344 and p = 0.0233, respectively) and CRP-low groups ( p < 0.0001 and p = 0.0001, respectively). Low levels of NLR and CRP at baseline were significantly associated with improved prognosis in patients treated with bevacizumab plus paclitaxel.