Abstract
ObjectiveTo investigate the prognostic value of derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) in patients with advanced HER2 positive breast cancer treated with trastuzumab emtansine.MethodsFifty one patients with advanced HER2 positive breast cancer who received T-DM1 treatment in Harbin Medical University Cancer Hospital were selected. The clinical data and blood test indexes were collected, and the ROC curve determined the optimal cut-off value. Kaplan-Meier survival curve and Cox regression model was used to analyze the effect of different levels of dNLR,LDH,LNI (dNLR combined with LDH index) before and after T-DM1 treatment on the survival of patients.ResultsThe median PFS and OS of the patients with advanced HER2 positive breast cancer who received T-DM1 treatment were 6.9 months and 22.2 months, respectively. The optimal cut-off value of LDH and dNLR before T-DM1 treatment was 244 U / L (P = 0.003) and 1.985 (P = 0.013), respectively. Higher LDH and dNLR were significantly correlated with shorter median PFS and OS (P < 0.05). The median PFS of patients with LNI (0), LNI (1) and LNI (2) were 8.1 months, 5.5 months and 2.3 months, respectively, P = 0.007. Univariate and multivariate analysis showed that LDH > 244 U / L, dNLR > 1.985, LNI > 0, ECOG ≥1 and HER-2 (IHC2 +, FISH+) before the T-DM1 treatment were the poor prognostic factors. LDH uptrend after the T-DM1 treatment also predicted poor prognosis.ConclusionSerum LDH > 244 U / L and dNLR > 1.985 before the T-DM1 treatment were prognostic risk factors for patients with advanced HER2 positive breast cancer receiving T-DM1 treatment. The higher LNI score was significantly associated with shorter PFS and OS. LDH uptrend after T-DM1 treatment was also related to the poor prognosis.
Highlights
Breast cancer is the most common cancer among women in the world
The present study aims to evaluate the prognostic significance of lactate dehydrogenase (LDH) and derived neutrophil to lymphocyte ratio (dNLR) in patients with advanced human epidermal growth factor receptor 2 (HER2) positive breast cancer treated with Trastuzumab emtansine (T-DM1), and investigate whether LDH and dNLR was able to predict treatment response to T-DM1
We found that LDH > 244 U/L, dNLR> 1.985, LDH combined with dNLR index (LNI)(1) and LNI(2) before T-DM1 treatment were associated with shorter progression-free survival (PFS) (HR, 2.238(1.217–4.116), P = 0.01; 2.549(1.330– 4.888), P = 0.005; 2.260(1.130–4.522), P = 0.021; 3.193(1.438–7.091), P = 0.004) (Table 4), and overall survival (OS) (HR, 4.368(2.010–9.493), P < 0.001; 3.756(1.843–7.657), P < 0.001; 2.498(1.069–5.836), P = 0.035; 16.209(5.837– 45.011), P < 0.001) (Table 5)
Summary
20% of breast cancers over-express human epidermal growth factor receptor 2 (HER2). Li et al BMC Cancer (2022) 22:29 introduction of trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1). T-DM1 is an antibody-drug conjugate which combines trastuzumab and the cytotoxic drug DM1 via a nonreducible thioether linker and it has been recommended as the standard second-line therapy of advanced breast cancer [1], which was associated with an objective response of 43.6% (95% confidence interval [CI], 38.6 to 48.6) and a median duration of progression-free survival of 9.6 months when the drug was administered after trastuzumab and a taxane [2]. Despite most patients can be controlled with T-DM1, there are still some patients who do not respond to the treatment. Biomarkers that predict the treatment efficacy of T-DM1 remain unknown
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