Research Papers:

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, Ayako Yanai, Takehiro Yanagawa, Junichi Inatome, Chiyomi Egawa, Arisa Nishimukai, Kaori Takamoto, Takashi Morimoto, Yuichiro Kikawa, Hirofumi Suwa, Tomoe Taji, Ai Yamaguchi, Yuki Okada, Atsushi Sata, Reiko Fukui, Ayako Bun, Hiromi Ozawa, Tomoko Higuchi, Yukie Fujimoto, Michiko Imamura and Yasuo Miyoshi _

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Yoshimasa Miyagawa1, Ayako Yanai2, Takehiro Yanagawa2, Junichi Inatome2, Chiyomi Egawa2, Arisa Nishimukai3, Kaori Takamoto3, Takashi Morimoto3, Yuichiro Kikawa4, Hirofumi Suwa5, Tomoe Taji5, Ai Yamaguchi5, Yuki Okada5, Atsushi Sata1, Reiko Fukui1, Ayako Bun1, Hiromi Ozawa1, Tomoko Higuchi1, Yukie Fujimoto1, Michiko Imamura1 and Yasuo Miyoshi1

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: [email protected]

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


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.

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