ObjectiveTo summarize the progress in mechanisms of resistance to trastuzumab in treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer. MethodsBy searching Pubmed and CNKI, the literatures of mechanisms of resistance to trastuzumab in treating HER2-positive breast cancer were reviewed. ResultsThe possible mechanism of resistance to trastuzumab are thought to include HER2 gene amplification and high protein expression; impaired access of trastuzumab to HER2; bidirectional crosstalk between ER and HER2; HER2 downstream signal transduction pathway activation; expansion expression of other RTKs and membrane-associated receptors; alterations in apoptosis and cell cycle control as well as multi-gene mutation, etc. ConclusionsMechanisms of trastuzumab resistance in HER2-positive breast cancer is complicated, a better understanding will be achieved by comprehensive analysis of existing possible mechanisms. The outcome of HER2-positive breast cancer patients who developed resistance to trastuzumab will be improved by appropriate multi-target regime.
ObjectiveTo summarize the biological characteristics of human epidermal growth factor receptor 2 (HER-2/neu) gene, the expression and meaning of HER-2/neu gene in gastric cancer, and clinical application of targeted medicine of HER-2/neu gene in gastric cancer. MethodsRelated literatures about HER-2/neu gene and gastric cancer were retrieved for a review. ResultsHER-2/neu gene encoded human epidermal growth factor receptor, and it participated in the gene regulation of tumor cell proliferation, invasion, and metastasis through the downstream signal transduction pathway. Amplification of HER-2/neu gene or overexpression of HER-2 was closely bound up to the occurrence and development of gastric cancer, however, whether it could be used as independent prognostic factors of gastric cancer remained to be controversial. Several targeted medicine of HER-2/neu gene had applied to clinical at present, and all of them obtained good short-term effect. ConclusionHER-2/neu gene is a reliable target of gastric cancer and targeted medicine of HER-2/neu gene has a promising prospect.
ObjectiveTo summarize the correlation between human epidermal growth factor receptor 2 (HER2) gene expression and the efficacy of targeted therapy for patients with HER2-positive breast cancer, and to summarize the new progress in the study of HER2 gene copy number. MethodThe relevant literatures on researches of targeted therapy effectiveness for patients with HER2-positive breast cancer were retrieved and reviewed. ResultsHER2 gene copy number and HER2/centromere on chromosome 17 (CEP17) ratio were related to the prognosis of patients with HER2-positive breast cancer, and circulating tumor DNA sequencing was expected to be a predictive indicator of targeted therapy effectiveness. ConclusionHigher copy number of HER2 gene might be associated with a better prognosis of HER2-positive breast cancer, and HER2/CEP17 ratio and circulating tumour DNA are of some significances in evaluating treatment response of trastuzumab for patients with HER2-positive breast cancer.
Objective Investigate the effect and treatment prospects of urokinase-type plasminogen activator receptor（uPAR）in human epidermal growth factor receptor-2 （HER-2） positive breast cancer. Method Aricals related effect of uPAR in HER-2 positive breast caner were retrieved through Pubmed， and the role of uPAR was reviewed. Results uPAR played a very important role in the HER-2 positive breast cancer， anti-uPAR monomer or uPAR binding inhibitors could inhibit the growth， invasion and metastasis of breast cancer cells. Conclusion uPAR is one of the effective target for breast cancer， and it provides a new breakthrough in the treatment of HER-2 positive breast cancer.
ObjectiveTo analyze the clinicopathologic features and prognosis of breast cancer patients with low human epidermal growth factor receptor-2 (HER2) expression. MethodsThe breast cancer patients underwent initially surgical resection in the First Hospital of Shanxi Medical University from October 2015 to October 2017 and met the criterion of this study were retrospectively gathered. Based on the immunohistochemical / in situ hybridization detection results, the patients were divided into three subtypes of HER2 zero, low, and positive expressions, and the differences in the clinicopathologic characteristics, overall survival (OS) and disease-free survival (DFS) of the three subtypes of breast cancer patients were compared. At the same time, the risk factors affecting the OS and DFS of breast cancer patients with low HER2 expression were analyzed. ResultsA total of 315 eligible patients were gathered in this study, including 68 patients with HER2 zero expression, 121 patients with low HER2 expression, and 126 patients with positive HER2 expression. There were no statistic differences in the menstrual status, T stage, and histological classification between the breast cancer patients with low HER2 and positive HER2 expressions (P>0.05), but the proportions of the patients with lymph node metastasis, histological grade Ⅲ, negative hormone receptor (HR) and high Ki67 expression in the low HER2 expression patients were lower than those in the positive HER2 expression patients. And compared with HER2 zero expression breast cancer patients, the proportions of premenopausal / perimenopausal, T2–4, N1–3, histological grade Ⅱ, ductal carcinoma, negative HR, and low Ki67 expression patients in the breast cancer patients with low HER2 expression were higher (P<0.05). While the survival curves of OS and DFS by Kaplan-Meier method had no statistic differences among the three subtypes of the breast cancer patients (χ2=0.070, P=0.966; χ2=0.362, P=0.835). The multivariate analysis results by Cox proportional hazards regression found that the low HER2 expression breast cancer patients with histological grade Ⅲ and negative HR had the higher risks of OS and DFS shortening (P<0.05). In addition, the risk of DFS shortening in the patients with T stage 2–4 and N stage 1–3 was increased (P<0.05). ConclusionsFrom the results of this study, breast cancer patients with low HER2 expression is different from the other two subtypes of breast cancer in terms of clinicopathologic characteristics. However, there are no statistical significances in comparing the OS and DFS of three types of breast cancer patients, but it is found that histological grading and HR are related to the OS and DFS of breast cancer patients with low HER2 expression, and it is also found that T stage and N stage are related to the DFS of breast cancer patients with low HER2 expression, so more attentions should be paid to the treatment plans.
Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.
ObjectiveTo summarize and analyze the long-term follow-up results and the recent researches of anti-epidermal growth factor receptor-2 (HER-2) dual targeted therapy for patients with human HER-2-positive breast cancer in terms of neoadjuvant, adjuvant, and salvage treatment so as to further improve the understanding of dual targeted therapy against HER-2 in clinical practice.MethodThe literatures on studies of dual targeted therapy for patients with HER-2-positive breast cancer in recent years were reviewed and analyzed.ResultThe anti-HER-2 dual targeted therapy could achieve a higher pathological complete response rate and better prognosis in the neoadjuvant therapy, as well as in adjuvant therapy and salvage treatment.ConclusionIn recent years, different combinations of targeted drugs in neoadjuvant, adjuvant, and salvage treatment of patients with HER-2-positive breast cancer have shown a benefit in clinical application, but more large sample prospective clinical researches are needed so as to find out optimal combination of targeted drugs with more benefits, less complications, and more economies.
ObjectiveTo explore the correlation between the texture features of gastric cancer plain CT images and the expression of HER2.MethodsA retrospective collection the datas of 62 patients with gastric cancer who underwent CT scans of the upper abdomen and (or) the whole abdomen from January 2017 to January 2021 in Leshan City People’s Hospital. The treatment method was surgery. The HER2 expression of gastric cancer tissue was detected after the operation. There were 45 male patients and 17 female patients. Lauren classification: 18 cases of intestinal type, 30 cases of diffuse type, and 14 cases of mixed type. Fifty-two cases were HER2 expression negative [age: (63.54±10.32) years], and 10 cases were HER2 expression positive [age: (61.70±11.70) years]. The MaZda module in the MaZda 4.6 version software was used to perform the image normalization, interest area delineation, texture feature extraction, and texture feature selection on the CT plain scan image, and perform texture feature discrimination and misjudgment rate analysis in the B11 module.ResultsThere was no correlation between HER2 expression and age, gender of patients and Lauren classification of tumors (P>0.05). The analysis methods of nonlinear discriminant analysis (NDA)/artificial neural network (ANN), linear discriminant analysis (LDA)/1-nearest-neighbor (1-NN), principal component analysis (PCA)/1-NN, and raw-data analysis (RDA)/1-NN can better correspond to the CT plain scan texture feature parameters of gastric cancer and the expression level of HER2.ConclusionsTexture analysis based on CT plain images has the potential to non-invasively detect the HER2 expression in gastric cancer. The best comprehensive performance texture discrimination method is NDA/ANN and LDA/1-NN.
Objective To investigate the relationship between the expressions of P-gp, GST-π and C-erbB-2 and clinicopathologic characteristics as well as prognosis in breast cancer. Methods The expressions of P-gp， GST-π and C-erbB-2 were detected by immunohistochemistry in 48 cases of breast cancer, and histopathologic characteristics as well as 5-year survival rate of these cases were analyzed. Results There was no significant difference in the expressions of P-gp and GST-π with age, histologic grade, number of lymph node metastasis and TNM stage of breast cancer ( P ＞ 0.05). There was significant difference in expression of C-erbB-2 with histologic grade, number of lymph node metastasis and TNM stage of breast cancer （ P ＜ 0.05）. Positive rate of P-gp expression in breast cancer with positive C-erbB-2 expression was remarkably higher than that in breast cancer with negative C-erbB-2 expression ( P ＜ 0.05) . Positive rate of GST-π and C-erbB-2 expression in survivals within 5 years was remarkably lower than that in deaths within 5 years ( P ＜ 0.01). Conclusion P-gp participates primary drug-resistance mechanism of breast cancer. The possibility of primary drug-resistance is higher in breast cancer with positive C-erbB-2 expression. The expression of C-erbB-2 helps to evaluate prognosis and the result of treatment in breast cancer.
ObjectiveTo investigate the influencing factors of total pathological complete response (tpCR) in newly treated human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients after neoadjuvant targeted chemotherapy, so as to provide more reference for the formulation of surgical plan and prognosis assessment. MethodsNinety-five newly treated HER2-positive breast cancer patients after neoadjuvant targeted chemotherapy were retrospectively chosen in the period from January 2021 to January 2023 in our hospital and all patients were divided into tpCR group (51 cases) and non-tpCR group (44 cases) according to whether tpCR was achieved after neoadjuvant targeted chemotherapy or not. Univariate and multivariate methods were used to evaluate the independent influencing factors of tpCR after neoadjuvant targeted chemotherapy in newly treated HER2-positive breast cancer patients. The prediction model based on the above independent influencing factors was constructed and the potential predictive efficacy of this model for tpCR after neoadjuvant targeted chemotherapy was evaluated. ResultsAmong 95 patients, 51 patients achieved tpCR after neoadjuvant targeted chemotherapy and 44 patients did not achieve tpCR. The results of the multivariate logistic regression model analysis showed that the patients with HER2 3+(OR=6.102, P=0.014), HER2+/hormone receptor– (HER2+/hormone receptor+ OR=0.129, P=0.006), and trastuzumab+pantomizumab treatment (OR=6.582, P=0.014) had higher tpCR rate, estrogen receptor 3+ (OR=0.122, P=0.0.033), progesterone receptor 3+ (OR=0.179, P=0.020), Ki-67 index of 15%–30% (OR=0.088, P=0.030) and 31%–60% (OR=0.066, P=0.017) had lower tpCR rate. The predicted area under the curve of this model was 0.881 [95%CI (0.815, 0.947)]. ConclusionsThe achievement of tpCR after new adjuvant treatment in newly diagnosed HER2 positive breast cancer patients is related to the expression level of HER2 in immunohistochemistry, molecular typing and new adjuvant targeted treatment scheme. At the same time, the prediction model based on these influencing factors can predict the effect of tpCR after new adjuvant treatment in patients to a certain extent.