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Introduction: Human epidermal growth factor receptor-2 (HER-2) low expression breast malignant tumors have become a research hotspot in recent years, but it is still unclear whether HER-2 low expression represents a special subtype of breast cancer. However, this molecular type requires more effective treatment regimens in the neoadjuvant therapy stage. Methods: This study enrolled breast cancer patients who were treated at Harbin Medical University Cancer Hospital with neoadjuvant treatment between October 2011 and May 2019 and was a single-center retrospective study. Results: A total of 1,053 breast cancer patients who received preoperative therapy, including 279 (26%) HER-2 low expression patients, were included in this retrospective study. The HER-2 low expression group had a higher proportion of patients under 50 years old than the other two molecular subtype groups (p = 0.047, 62.0% vs. 57.2% and 52.5%), and the percentage of patients with Ki67 index above 15% was lower than that in HER-2-negative and HER-2-positive patients (p < 0.001, 50.2% vs. 63.6% and 71.5%). Most of the patients with HER-2 low expression were hormone receptor (HR) positive (p < 0.001, 85.7% vs. 60.4% and 36.0%), and their pathologic complete response (pCR) rate after neoadjuvant therapy was significantly lower than that of HER-2-negative and HER-2-positive patients (p < 0.001, 5.7% vs. 11.8% and 20.5%). The results of the subgroup analysis showed HR-positive patients with HER-2 low expression had a lower pCR rate (p < 0.001, 4.6% vs. 14.6%) and objective response rate (p = 0.001, 77.8% vs. 91.0%) than HER-2-positive patients and had no significant difference in these rates compared to HER-2-negative patients. There were no significant differences in overall survival (OS) and disease-free survival (DFS) up to 67 months (the median follow-up time) among HER-2 low, HER-2-negative, and HER-2-positive patients. The results of Cox hazard proportional showed that the Ki67 index and T stage (T3) were independent influencing factors for DFS. In terms of OS, Ki67 index, P53, T stage, and objective response were independent influencing factors for OS in HER-2 low expression patients. Conclusions: In general, further studies are needed to confirm that HER-2 low expression is a special breast cancer molecular subtype. The efficacy of neoadjuvant therapy in patients with HER-2 low expression is relatively poor, and the efficacy of neoadjuvant therapy can predict the prognosis of patients with HER-2 low expression. [ABSTRACT FROM AUTHOR]

Purpose: Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is associated with the prognosis of several human malignancies. In this study, the role of LAPTM4B in the metastatic potential of breast cancer (BC) and its underlying molecular mechanisms were investigated. Methods: The relationship between LAPTM4B expression and axillary lymph node metastasis was determined in 291 BC specimens by immunohistochemistry. The expression of LAPTM4B in paired BC cells was overexpressed and inhibited to analyse the role of LAPTM4B in the aggressiveness of BC. Cell proliferation, migration and invasion were assessed in vitro. Metastasis-related protein levels were detected through Western blot. Results: Immunohistochemical staining demonstrated that high expression level of LAPTM4B was independently associated with axillary lymph node metastasis (odds ratio=2.428; 95%CI=1.333- 4.425; P=0.004). The LAPTM4B inhibition in MCF-7 cells inhibited cell proliferation, migration, invasion, and resulted in simultaneous downregulation of phosphorylated N-cadherin, vimentin, and upregulation of E-cadherin. By contrast, the LAPTM4B overexpression promoted cell proliferation, migration, invasion, and led to simultaneous upregulation of N-cadherin, vimentin, and downregulation of E-cadherin in T47D cells. Conclusions: High expression level of LAPTM4B predicts tumor metastatic potential in patients with BC. Our results provide the first evidence of the role of LAPTM4B as an Epithelial-mesenchymal transition (EMT) inducer that promotes aggressiveness in BC cells. [ABSTRACT FROM AUTHOR]

Background and Purpose: The modified systemic inflammation score (mSIS) system, which is constructed based on the neutrophil to lymphocyte ratio (NLR) and albumin (Alb), has not been applied to evaluate the prognosis of malignant breast cancer patients who underwent neoadjuvant chemotherapy (NAC). The present study aimed to explore the relationship between the mSIS and overall survival (OS), disease-free survival (DFS) and pathological complete response (pCR).Methods: A total of 305 malignant breast tumor patients who underwent NAC were incorporated into this retrospective analysis. We determined OS and DFS using K-M survival curves and the log-rank test. The relationship between the mSIS and OS and DFS was evaluated by a Cox regression model. A nomogram was constructed based on Cox regression analysis.Results: Patients in the mSIS low-risk group had better 5- and 8-year OS rates than those in the mSIS high-risk group (59.8% vs. 77.0%; 50.1% vs. 67.7%; X2 = 8.5, P = 0.0035, respectively). Patients in the mSIS (1 + 2 score) + pCR subgroup had the highest 5- and 8-year OS and disease-free survival (DFS) rates (OS: 55.0% vs. 75.7% vs. 84.8, 42.8% vs. 65.7% vs. 79.8%, X2 = 16.6, P = 0.00025; DFS: 38.8% vs. 54.7% vs. 76.3%, 33.3% vs. 42.3 vs. 72.1%, X2 = 12.4, P = 0.002, respectively). Based on the mSIS, clinical T stage and pCR results, the nomogram had better predictive ability than the clinical TNM stage, NLR and Alb.Conclusions: mSIS is a promising prognostic tool for malignant breast tumor patients who underwent NAC, and the combination of mSIS and pCR is helpful in enhancing the ability to predict a pCR. [ABSTRACT FROM AUTHOR]