Junnan Xu, Mingxi Jing, Yan Wan, TaoSun

Department of Internal Oncology, Shenyang LiaoningCancer Hospital & Institute

Objective: Trastuzumab has been shown to medicate antibodydependent cell mediated cytotoxicity (ADCC) and inhibit HER-2. AssociatedNatural Killer (NK) cell with ADCC effect in metastatic breast cancer remainsunknown. In this study, we examined to characterize the impact of NK cell onoutcomes of trastuzumab in HER-2 positive breast cancer patients. Method: Weevaluated associations between NK cell doses and outcomes of trastuzumab in 200patients with HER-2 positive breast cancer. The percentages of circulatingimmune cell subsets including Natural Killer (NK) cells were quantified bymultiparametric flow cytometry. Progression-Free Surivial (PFS1) and secondaryPFS (PFS2) after discontinue trastuzumab due to progression disease wereanalyzed. A high NK cell was defined as ≥ 28%, which was approximatedly theupper tertile value. Result: Forty-seven patients with HER-2/neuamplified metastatic breast cancer receiving trastuzumab combined withchemotherapy. High NK cell doses were significant associated with improvedprogression-free survival 1 (HR, 0.67; P=0.026) and the sum of PFS1 andPFS2 (HR, 0.87; P=0.04), without a significant increase in overallsurvival (HR, 0.89; P=0.06). A cutoff level of 28% NK cells optimallysegregated patients receiving NKhigh and NKlow with differing PFS (14.4 mos VS9.2 mos, P=0.007). Compared with high NK cell doses non-treatment oftrastuzumab in HER-2 positive metastatic breast cancer, overall survival wassignificantly better for treatment of trastuzumab (P =0.03). In addition, ADCCeffect could be predicted by measuring the proportion of NK cell dose. However,whether CD8+ and CD4+ T cell also predicted ADCC effect and improved survivalby trastuzumab still be unknown. Conclusion: Higher NK cell dose, whichwas restricted to HER-2 positive metastatic breast cancer receivingtrastuzumab, predicted better clinical benefit and ADCC effect.

Key Words: metastatic breast cancertrastuzumab