A role for peripheral natural killer (NK) cell activity in the response to neoadjuvant chemotherapy in patients with breast cancer.

e12073 Background: Tumor-infiltrating lymphocytes (TILs) have prognostic and potentially predictive value in patients (pts) under neoadjuvant chemotherapy (NAC), especially in human epidermal growth factor receptor 2 (HER2)-positive and triple negative (TN) breast cancer. NK cells can spontaneously recognize and kill cancer cells, and lower levels of NK cells are associated with an increased risk of death from breast cancer. We assessed peripheral NK cell activity for potential associations with pathologic therapeutic response and cancer subtype. Methods: Twenty eight pts with stage II-IV breast cancer were treated with NAC from July 2012 to Sept. 2015 in our clinic using albumin-bound paclitaxel (nab-PTX)/fluorouracil/epirubicin/cyclophosphamide (FEC), nab-PTX/FEC/trastuzumab (HER), docetaxel (DTX)/FEC, FEC/DTX, FEC/DTX/HER. Peripheral NK cell activity was measured before and after NAC. Results: Increased NK cell activity was observed in 16 pts, but was decreased in 12 pts. TILs were found to be present to a lesser extent in the primary lesion (1-20%) after NAC. Six factors including median age, stage, > G2 response, disappearance of axillar lymph node metastasis (Ax+), nuclear grade, and Ki-67-positivity were considered in univariate analyses. Disappearance of Ax+ was found to be significantly associated with increased NK cell activity (p = 0.02). Based on multivariate analysis including the two factors > G2 and disappearance of Ax+, increased NK cell activity was significantly associated with the latter (OR = 8.00, 95% CI = 1.24-51.50, p = 0.02). HER2 type was significantly associated with increased NK cell activity (OR = 7.85, 95% CI = 1.10-56.12, p = 0.03), and TN tended to be associated (p = 0.08). A high Ax+ disappearance rate was observed in association with HER2 and TN type (p = 0.002). Conclusions: Disappearance of Ax+ following NAC tended to be associated with increased NK cell activity after NAC, mostly likely due to activation of NK cell-mediated tumor immunosurveillance and inhibition of metastases. HER-induced antibody-dependent cellular cytotoxicity was especially likely to be involved in this effect.