Cardioprotective Effect of Statins in Patients With HER2-Positive Breast Cancer Receiving Trastuzumab Therapy

2019 ◽  
Vol 35 (2) ◽  
pp. 153-159 ◽  
Author(s):  
Oscar Calvillo-Argüelles ◽  
Husam Abdel-Qadir ◽  
Maria Michalowska ◽  
Filio Billia ◽  
Sivisan Suntheralingam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cardioprotective Effect ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Trastuzumab Therapy ◽  
Positive Breast Cancer

scholarly journals UCP-2 inhibitor enhanced the efficacy of trastuzumab against HER2 positive breast cancer cells

2021 ◽  
Author(s):  
Jun Hua ◽  
Zhe Zhang ◽  
Lili Zhang ◽  
Yan Sun ◽  
Yuan Yuan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Neoadjuvant Therapy ◽  
Needle Biopsy ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Trastuzumab Treatment ◽  
Her2 Positive Breast Cancer ◽  
Trastuzumab Therapy ◽  
Positive Breast Cancer

Abstract Purpose This study aimed to investigate the possibility of UCP-2 inhibitor in reducing acquired resistance of trastuzumab to improve the outcome of patients receiving trastuzumab therapy by exploring the relationship between UCP-2 expression and HER2 signaling pathway and examining whether UCP-2 expression was modulated by trastuzumab treatment. Methods 32 women diagnosed with primary HER2-positive breast cancer were recruited in this study. Needle biopsy was obtained from patients before they received at least four cycles neoadjuvant therapy containing trastuzumab in combination with chemotherapy. Surgical tumor biopsy was obtained during surgical procedure after the neoadjuvant therapy. Levels of HER2 phosphorylation and UCP-2 expression were detected by immunohistochemistry (IHC) and compared between tumor needle biopsy tissue and surgical tumor samples of these patients, as well as in BT474 breast cancer cells before and after trastuzumab treatment. HER2-selective phosphorylation/kinase activity inhibitor ONT-380 was used to identify the correlation between HER2 phosphorylation level and UCP-2 expression. UCP-2 inhibitor Genipin was then used to evaluate the apoptosis index in BT474 cells treated with trastuzumab. Results UCP-2 expression was significantly elevated in surgical tumor samples from breast cancer patients receiving trastuzumab in a neoadjuvant setting. We further confirmed our findings in HER2-positive BT474 cell line and found that trastuzumab treatment induced phosphorylation of HER2 and the overexpression of UCP-2, and the latter can be reversed by HER2 selective kinase inhibitor ONT-380. Moreover, UCP-2 inhibitor Genipin significantly enhanced the proliferation suppression effects of trastuzumab and markedly promoted apoptosis. Conclusion Taken together, our study identified UCP-2 as a novel therapeutic target for HER2 positive breast cancer and UCP-2 inhibitor may have great potential to enhance the response rate and efficacy of trastuzumab therapy.

scholarly journals Immune Effective Score As A Predictor Of Response To Neoadjuvant Trastuzumab Therapy And A Prognostic Indicator For HER2-positive Breast Cancer

2021 ◽  
Author(s):  
Xueying Wu ◽  
Chenyang Zhang ◽  
Jing-wei Xiong ◽  
Henghui Zhang
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Clinical Outcomes ◽  
Killer Cell ◽  
Therapy Response ◽  
Gene Set Enrichment Analysis ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Trastuzumab Therapy ◽  
Positive Breast Cancer

Abstract Background: HER2-positive breast cancer (BC) is a highly aggressive phenotype and accounts for 15–20% of all BC cases. The role of the host immune features in predictive response to anti-HER2 therapies and prognosis in BC is already suggested. We aimed to develop a predictive and prognostic model and examine its relevance to the clinical outcomes of patients with HER2-positive BC.Methods: Based on the single-sample gene set enrichment analysis (ssGSEA) scores of the signatures related to neoadjuvant trastuzumab therapy response, an immune effective score (IES) was constructed using principal component analysis algorithms. A bioinformatic analysis using 4 independent cohorts (GSE66305, n=88; GSE130786, n=110; TCGA, n=123; METABRIC, n=236) established associations between IES and clinical outcomes.Results: Genes associated with neoadjuvant trastuzumab therapy response enriched in pathways related to antitumor immune activities, including T cell receptor signaling pathway, Natural killer cell-mediated cytotoxicity and NF−kappa B signaling pathway. IES was demonstrated to be a predictive biomarker to neoadjuvant trastuzumab therapy benefits (GSE66305: area under the curve (AUC) = 0.804; GSE130786: AUC = 0.704). In addition, IES was identified as an independent prognostic factor for overall survival (OS) in the TCGA cohort (P = 0.036, hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.449–0.97) and METABRIC cohort (P = 0.037, HR: 0.9, 95% CI: 0.81–0.99).Conclusions: The IES has a predictive value for response to neoadjuvant trastuzumab therapy and independent prognostic value for HER2-positive breast cancer.

Trastuzumab use at relapse after adjuvant trastuzumab therapy in HER2-positive breast cancer.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 575-575 ◽  
Author(s):  
I. Lang ◽  
R. Bell ◽  
F. Feng ◽  
R. I. Lopez ◽  
J. Jassem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Her2 Positive Breast Cancer ◽  
Trastuzumab Therapy ◽  
Positive Breast Cancer
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