Abstract P3-10-19: Significance of baseline neutrophil-to-lymphocyte ratio for progression-free survival of patients with HER2-positive locally advanced and metastatic breast cancer treated with trastuzumab emtansine
Authors: Imamura M , Morimoto T , Egawa C , Miyagawa Y , Miyoshi Y 
Published: May 2019

Abstract
Purpose The prognosis of human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancers (MBCs) has dramatically improved due to the introduction of trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1). The efficacy of T-DM1 is prolonged for some patients; however, the predictive factors remain unknown. There is a report that T-DM1 induced antitumor immunity in patients treated with neoadjuvant therapy, with tumor infiltrating lymphocytes (TILs) increasing after the administration of T-DM1. Based on these observations, the benefits of T-DM1 for prognosis may be mediated by an immune reaction against breast cancers, at least in part. As an indicator of cancer immunity, in addition to TILs, the neutrophil-to-lymphocyte ratio (NLR) has been established in early breast cancers. In the present study, we investigated the usefulness of the NLR for treatment efficacy of T-DM1 in HER2-positive MBCs. Methods Fifty-three advanced or metastatic breast cancers treated with T-DM1 were retrospectively recruited from three institutes. The NLR in the peripheral blood was measured at baseline (just before the start of T-DM1) and after one cycle (just before the start of cycle 2). The cutoff value of the NLR was set at 2.56 (median value) and progression-free survival (PFS) and overall survival (OS) according to NLR levels were evaluated. Results The PFS of patients with NLR-low at baseline (NLR&lt;2.56; n=26; median, not reached) was significantly better than that of patients with NLR-high (NLR≥2.56; n=27; median, 4.13 months; hazard ratio [HR], 0.226; 95% confidence interval [CI], 0.112-0.493; p=0.0001). There was a significant association between improved OS and a low NLR (HR, 0.384; 95% CI, 0.170-0.910; p=0.0296). In the subgroup analysis, patients with NLR-low consistently had improved PFS compared to those with NLR-high irrespective of the number of prior chemotherapy regimens, prior trastuzumab use, visceral metastasis, estrogen receptor status, and HER2 immunohistochemical staining score. According to univariable analysis of each clinical and biological factor for PFS, the NLR-low group was solely and significantly associated with favorable PFS compared with the NLR-high group (HR, 0.226; 95% CI, 0.112-0.493; p=0.0001). The NLR at baseline was significantly decreased (p=0.0010) and lymphocyte count was significantly increased after one cycle treatment (p=0.0005). Interestingly, the PFS of patients whose NLR was high at baseline but changed to low after one cycle (n=12; median PFS, 6.47 months) was better than that of patients with a consistently high NLR (n=14; median PFS, 3.27 months). Conclusion and Discussion A low baseline NLR was found to be significantly associated with improved PFS for patients treated with T-DM1. Interestingly, lymphocyte count was significantly increased in patients in the NLR-low group but not in the NLR-high group after one cycle treatment. Although detailed mechanisms remain unknown, the treatment efficacy of T-DM1 may be partly mediated by immunoreaction on the basis of present data. A low baseline NLR appears to be beneficial for treatment with T-DM1 in HER2-positive breast cancers.
Citation Format: Imamura M, Morimoto T, Egawa C, Miyagawa Y, Miyoshi Y. Significance of baseline neutrophil-to-lymphocyte ratio for progression-free survival of patients with HER2-positive locally advanced and metastatic breast cancer treated with trastuzumab emtansine [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-19.