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.
Objective To analyze the factors associated with the adoption of targeted therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and to generate evidence to inform decision-making on public security policy regarding innovative anticancer medicines for the benefit of patients. Methods The study population comprised female patients diagnosed with HER2-positive breast cancer and treated at Fujian Cancer Hospital from 2014 to 2020. The patients were eligible for targeted therapy. The demographic and sociological characteristics and clinical information of patients were extracted from the hospital information system. We performed binary logistic regression analysis of factors associated with the adoption of targeted therapy in patients with HER2-positive breast cancer. We also divided the participants into two groups according to their tumor stage for subgroup analysis. Results A total of 1 041 female patients with HER2-positive breast cancer were included, among them, 803 received targeted therapy. In September 2017, molecular-targeted medicines for HER2-positive breast cancer began to be included in the local basic health insurance program. Only 282 (35.1%) patients adopted targeted therapy before September 2017, after which this number increased to 521 (64.9%). Among the patients who adopted targeted therapy, most were formally employed (45.8%) and enrollees of the urban employee health insurance program (66.0%). Among those who did not adopt targeted therapy, most were unemployed (42.4%) and enrollees of the resident health insurance program (50.0%). Binary logistic regression analysis revealed that patient occupation, gene expression of estrogen receptor, tumor stage, surgery or not, radiotherapy or not, and undergoing treatment before or after September 2017 were correlated with the adoption of targeted therapy (P<0.05). Conclusions Inclusion of targeted medicines for HER2-positive breast cancer in the health insurance program substantially increased the overall administration of these therapies. Individual affordability is a critical factor associated with the application of targeted therapy in eligible patients. Future policies should enhance the public security of patients with a relatively weak ability to pay and provide insurance coverage for innovative anti-cancer medicines.
Objective To investigate the clinicopathological characteristics of HER2 protein expression in different degrees in human epidermal growth factor receptor 2 (HER2) negative breast cancer and the factors related to the efficacy of neoadjuvant chemotherapy in breast cancer with low HER2 expression. Methods The clinicopathological data of 161 patients with HER2-negative breast cancer who received neoadjuvant chemotherapy in the Department of Breast Surgery, Affiliated Hospital of Southwest Medical University from March 2019 to March 2022 were retrospectively collected. The difference of clinical and pathological characteristics of patients with different levels of HER2 protein expression were analyzed, and the factors influencing the pathological complete remission (pCR) rate of breast cancer patients with low HER2 expression after neoadjuvant chemotherapy with unconditional logistic regression model were analyzed. Results Among 161 HER2 negative breast cancer patients, 108 cases were low HER2 expression, accounting for 67.1%. Compared with those with zero expression of HER2 [immunohistochemistry (IHC) 0], the patients with low HER2 expression had higher axillary lymph node metastasis rate (P=0.048), lower histological grade (P=0.006), and higher proportion of positive hormone receptor expression (P<0.001). There was no significant difference in pCR rate among the HER2 IHC 0, IHC 1+ and IHC 2+ / in situ hybridization (ISH)– (P=0.099) , and the pCR rate of low expression of HER2 was lower than that of zero expression of HER2 in the general population and Luminal subgroup, and the difference was statistically significant (P<0.05). There was no significant difference in triple negative breast cancer subgroup (P=0.814). The logistic regression analysis showed that age, histological grade and estrogen receptor expression status were independent influencing factors for pCR rate after neoadjuvant chemotherapy with low HER2 expression (P<0.05). Conclusions Different degrees of HER2 protein expressions in patients with HER2-negative breast cancer have unique clinicopathological characteristics. The pCR rate of neoadjuvant chemotherapy in patients with low HER2-expression breast cancer is lower than that in patients with zero HER2-expression breast cancer. Age, histological grade and estrogen receptor expression status are independent factors influencing the pCR rate of neoadjuvant chemotherapy in patients with low HER2-expression breast cancer.
Objective To compare the efficacy and safety of different cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer. Methods Randomized controlled trials (RCTs) on CDK4/6i for the treatment of HR+/HER2− metastatic or advanced breast cancer were retrieved from databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed, with the search period ranging from database inception to August 2023. Bayesian network meta-analysis was conducted using R 4.2.0 software. Results A total of 18 RCTs from 25 articles, involving 8 031 patients and 11 treatment regimens, were included. There was no significant difference in progression-free survival (PFS) or overall survival (OS) among different CDK4/6i+ET combinations. The highest cumulative probability for PFS was observed with dalpiciclib (DAL)+fulvestrant (FUL), while ribociclib (RIB)+FUL ranked first for OS. In terms of efficacy, abemaciclib (ABE)+aromatase inhibitors (AI) and ABE+FUL ranked first in objective response rate and clinical benefit rate, respectively. Regarding safety, statistically significant difference in grade 3-4 adverse events was observed among certain types of CDK4/6i (P<0.05). Conclusion Current evidence suggests that CDK4/6i+ET is superior to ET alone for the treatment of HR+/HER2− advanced/metastatic breast cancer. Different CDK4/6i+ET combinations demonstrate comparable or similar efficacy; however, the incidence of adverse reactions is higher with combination therapy. Treatment regimens should be selected based on individual conditions.
ObjectiveTo compare clinicopathologic characteristics and prognosis between HER2-low and HER2-negative patients with stage T1 and T2 triple-negative breast cancer (TNBC). MethodsThe patients with stage T1 and T2 TNBC treated at the Affiliated Hospital of Southwest Medical University from June 2019 to June 2021 were retrospectively collected. The clinicopathologic features were analyzed using two-sided Chi-square test. Multivariate binary logistic regression identified risk factors for 3-year postoperative recurrence/metastasis. Kaplan-Meier survival curves was used to compare 3-year disease-free survival (DFS) between the TNBC patients with HER2-low and HER2-negative. The statistical significance was defined as α=0.05. ResultsA total of 126 patients with stage T1 and T2 TNBC were enrolled, 63 were HER2-negative and 63 HER2-low. Compared with HER2-negative patients, HER2-low patients demonstrated significantly higher proportions of: Age ≥50 years old, postmenopausal status, lymphovascular invasion (P<0.05). HER2 expression level and axillary lymph node metastasis were the independent risk factors for 3-year postoperative recurrence/metastasis in the patients with stage T1 and T2 TNBC (P<0.05). The patients with HER2-low expressing demonstrated significantly inferior 3-year DFS compared to patients with HER2-negative (χ2=7.741, P=0.005). ConclusionsFindings of this study suggest that among patients with stage T1 and T2 TNBC, HER2-low expression is associated with advanced age (≥50 years), menopausal status, and lymphovascular invasion. It may serve as an indicator of a distinct biologic subgroup or unfavorable pathologic characteristics. Patients with stage T1 and T2 TNBC who have HER2-low expression and positive axillary lymph node metastasis require close monitoring for recurrence/metastasis within 3 years postoperatively.
ObjectiveTo systematically evaluate the correlation of amplification of human epidermal growth factor receptor 2 (HER2) with the clinicopathological characteristics and prognosis of colorectal cancer patients.MethodsPubMed, EMbase, Cochrane Library, Chinese Biomedical Literature Database (CBM), Wanfang, and other databases were searched, and cohort studies focused on the relationship between HER2 amplification and clinicopathological characteristics and prognosis of colorectal cancer patients were included. The retrieval time limit was from October 2020, and RevMan 5.4 software was used for meta-analysis.ResultsA total of 9 studies (11 cohorts) were included for meta-analysis of 7 209 patients with colorectal cancer. Results of the meta-analysis showed that HER2 amplification was not associated with overall survival [HR=1.10, 95%CI (0.98, 1.24), P=0.11]. HER2 amplification was not correlated with gender [OR=0.98, 95%C1 (0.74, 1.31), P=0.90] and tumor differentiation [OR=0.80, 95%C1 (0.49, 1.32), P=0.39], but correlated with the tumor location [OR=1.85, 95%C1 (1.01, 3.37), P=0.04], RAS wild-type gene [OR=6.36, 95%C1 (3.41, 11.87), P<0.000 01], TNM stage [OR=0.45, 95%C1 (0.32, 0.64), P<0.000 01], lymph node metastasis [OR=1.54, 95%C1 (1.12, 2.13), P=0.008], and the depth of tumor invasion [OR=0.17, 95%C1 (0.05, 0.55), P=0.003].ConclusionCurrent evidence shows that HER2 amplification is not associated with OS in patients with colorectal cancer, but associated with tumor infiltration, lymph node metastasis, TNM stage, tumor site, and RAS genotype.
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 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.
ObjectiveTo investigate the expression of epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) and its relation with clinicopathologic features. MethodsA computer search of PubMed, Web of Science, CNKI, Wanfang Data, and VIP databases were conducted to select clinical studies on EGFR expression in the TNBC according to the inclusion and exclusion criteria, and the search period was from database establishment to January 2022. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the literature before conducting meta-analysis using RevMan 5.4 software. ResultsA total of 28 studies including 7 956 patients were included. The results of meta-analysis showed that the positive rate of EGFR expression in the TNBC patients was higher than that in the non-TNBC patients [OR=5.16, 95%CI (4.04, 6.58), P<0.000 01], and the proportions of patients with axillary lymph node metastasis [OR=3.11, 95%CI (1.56, 6.19), P=0.001] and with tumor diameter >2 cm [OR=2.09, 95%CI (1.18, 3.72), P=0.01] in the patients with EGFR positive were higher than those the patients with EGFR negative, no correlation was found that the proportion of patients with histological WHO classification 3 between the patients with EGFR positive expression and EGFR negative expression (P=0.07). ConclusionFrom the results of this meta-analysis, EGFR expression might be associated with the occurrence, development, and metastasis of patients with TNBC.
ObjectiveTo analyze the clinicopathologic characteristics and prognosis of human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with different expression status of estrogen receptor (ER). MethodsThe patients with HER2-negative breast cancer met the inclusion and exclusion criteria and were treated in the Affiliated Hospital of Southwest Medical University from January 1, 2017 to December 31, 2019 were retrospectively collected, and then were assigned into 3 groups according to the ER expression status: ER-negative (ER expression positive rate <1%) group, ER-low expression (ER expression positive rate 1%–10%) group, and ER expression positive rate >10% group. The differences of clinicopathologic characteristics, therapy, and prognosis among the 3 groups were compared. And the risk factors affecting recurrence and metastasis of patients with ER-low expression were analyzed by Cox proportional hazards regression model. ResultsA total of 610 patients with HER2-negative breast cancer were included in this study, including 130 patients in the ER-negative group, 48 patients in the ER-low expression group, and 432 patients in the ER expression positive rate >10% group. The Bonferroni method was used to correct the test level after pairwise comparison, it was found that the histological grade was later (P<0.001, P=0.023) and the Ki-67 expression was higher (P<0.001, P=0.023) in the ER-negative group and ER-low expression group as compared with the ER expression positive rate >10% group; The proportion of the patients receiving chemotherapy in the ER-negative group was higher than that of the ER expression positive rate >10% group (χ2=10.310, P=0.001), while which had no statistical difference between the ER-low expression group and the ER-negative group or the ER expression positive rate >10% group (Fisher exact probability method, P=1.000; χ2= 3.585, P=0.058); The proportion of patients receiving endocrine therapy in the ER-low expression group was higher than that in the ER-negative group (χ2=36.333, P<0.001) and lower than the ER expression positive rate >10% group (χ2=246.996, P<0.001). The difference in disease-free survival (DFS) curves among 3 groups was statistically significant (χ2=46.805, P<0.001); There were no statistical differences in the overall survival (OS) curve and DFS curve between the ER-negative group and the ER-low expression group (Two stage test, P=0.786; χ2=1.141, P=0.286), and which in the ER expression positive rate >10% group were significantly better than thoses in the ER-negative group (χ2=10.137, P=0.001; χ2=39.344, P<0.001) and the ER-low expression group (χ2=4.075, P=0.044; χ2=31.911, P<0.001). The results of multivariate Cox proportional hazards regression analysis showed that N1 and N2 [N0 as reference: RR (95%CI)=7.740 (1.939, 30.897), P=0.004; RR (95%CI)=9.513 (1.990, 45.478), P=0.005) and T3 [T1 as reference: RR (95%CI)=27.357 (2.188, 342.041), P=0.010] increased the probabilities of recurrence and metastasis HER2-negative breast cancer patients with ER-low expression. ConclusionsAccording to results of this study, patients with HER2-negative breast cancer showed certain differences in histological grade and Ki-67 expression among patients with three different ER expression status, but no statistical difference is found between ER-low expression and ER-negative breast cancer, and the prognoses of both are worse than that of ER expression positive rate >10% breast cancer patients. Lymph node metastasis and larger tumor are risk factors affecting recurrence and metastasis in ER-low expression breast cancer patients.