Abstract
The efficacy of trastuzumab emtansine (T-DM1) is prolonged for some patients; however, the predictive factors remain unknown. We focused on a peripheral blood biomarker, the neutrophil-to-lymphocyte ratio (NLR), regarding T-DM1 treatment efficacy. 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 and after one cycle. The cutoff value of the NLR was set at median value 2.56. The progression-free survival (PFS) of patients with NLR-low at baseline (n = 26; median, not reached) was significantly better than that of patients with NLR-high (n = 27; median, 4.13 months; hazard ratio [HR], 0.226; 95% confidence interval [CI], 0.112–0.493; p = 0.0001). Longer overall survival was significantly associated with 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 longer PFS compared to those with NLR-high irrespective of the number of prior chemotherapy regimens, prior trastuzumab, visceral metastasis, estrogen receptor status, and human epidermal growth factor receptor 2 (HER2) score. Although detailed mechanisms remain unknown, treatment efficacy of T-DM1 may be partly mediated by activation of the immune system. Low baseline NLR appears to be beneficial for treatment with T-DM1 in HER2-positive breast cancers.
Highlights
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)[1]
Among 53 patients treated with T-DM1, 26 and 27 patients were classified into neutrophil-to-lymphocyte ratio (NLR)-low (
There was no significant association between other clinicopathological characteristics, including menopausal status, Eastern Cooperative Oncology Group Performance Status (ECOG PS), disease-free interval, disease control during 1st line treatment, estrogen receptor (ER) status, HER2 immunohistochemical score (IHC) score (2+ or 3+), number of metastatic sites, metastatic sites, prior endocrine therapy, brain metastasis, number of prior chemotherapies, prior anthracycline, prior taxene, prior pertuzumab, prior lapatinib, and reason of treatment discontinuation
Summary
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)[1]. HER2-positive breast cancer patients with higher intratumor HER2 mRNA levels had lower risk of death when treated with T-DM1 than when with capecitabine plus lapatinib (HR, 0.53; 95% CI, 0.37–0.76). Müller P et al reported that T-DM1 induced antitumor immunity in patients treated with neoadjuvant therapy, with tumor infiltrating lymphocytes (TILs) increasing after the administration of T-DM110 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. We recently reported the usefulness of the NLR for treatment efficacy in primary advanced and recurrent patients treated with eribulin[16]. In the present study, we investigated the usefulness of the NLR and PLR for treatment efficacy of T-DM1 in HER2-positive primary advanced and recurrent breast cancers
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