Pharmacoeconomic evaluation of trastuzumab biosimilars versus original drug in the treatment of recurrent/metastatic HER-2 positive breast cancer / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of trastuzumab biosimilars （Hanquyou） versus original drug （Hesaiting） in the treatment of recurrent/metastatic human epidermal growth factor receptor-2 （HER-2） positive breast cancer. METHODS A partitional survival model was constructed based on the NCT03084237 trial data. The simulation period was 3 weeks， and the simulation time was 10 years. Using costs and quality-adjusted life year （QALY） as the output indicator， the cost- utility analysis method was used to evaluate the cost-effectiveness of the two schemes mentioned above. Univariate and probabilistic sensitivity analyses were performed to verify the robustness of the basic analysis. RESULTS The costs of the trastuzumab biosimilars group and original drug group were 111 516.72 yuan and 111 122.30 yuan respectively， with health utility values of 1.52 QALYs and 1.36 QALYs， and ICER of 2 465.12 yuan/QALY， which were less than 3 times China’s per capita gross domestic product （GDP） in 2023 as the threshold for willingness-to-pay （WTP） （268 200 yuan/QALY）. Univariate sensitivity analysis showed that the cost of the trastuzumab biosimilars and original drug had a great impact on the ICER. The probabilistic sensitivity analysis showed that the probability of trastuzumab biosimilars being cost-effective was 100% at WTP threshold of 14 902 yuan/QALY. CONCLUSIONS When WTP threshold is 3 times China’s GDP in 2023 （268 200 yuan/QALY）， compared with original drug， trastuzumab biosimilars have good cost-effectiveness in the treatment of recurrent/metastatic HER-2 positive breast cancer.

The preoperative prediction value of dual-energy CT-based nomogram in human epidermal growth factor receptor 2 status of breast cancer / 实用放射学杂志

Objective To explore the application value of the nomogram based on dual-energy CT in preoperative evaluation of human epidermal growth factor receptor 2(HER-2)status in patient with breast cancer.Methods A total of 269 patients with pathologically confirmed breast cancer were retrospectively collected and randomly divided into a training cohort(n=189)and a validation cohort(n=80)at a ratio of 7︰3.The dual-energy CT parameters and clinical features of all patients were measured and collected.Varia-bles with significant difference in univariate analysis were included in the multivariate logistic analysis to obtain independent risk fac-tors related to HER-2 status,with establishing a nomogram model.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive performance of the nomogram.Results There was a significant difference in axillary lymph node enlargement between the two groups(P<0.05).The venous phase iodine concentration(IC)and normalized iodine concentration(NIC)in the HER-2 positive group were significantly higher than those in the HER-2 negative group(P<0.05).Axillary lymph node enlargement,venous phase IC,and venous phase NIC were the independent risk factors for predicting HER-2 status in breast cancer.The nomogram con-structed from the above features exhibited good predictive performance,with area under the curve(AUC)of 0.856 and 0.834 in the training and validation cohorts,respectively.Conclusion The nomogram based on dual-energy CT has a high predictive value for HER-2 status in breast cancer patients.

Correlation analysis between the expressions of HER2 and CA153 and the VTIQ technical parameter in patients with breast cancer / 中国医学装备

Objective:To analyze the correlation between the expressions of human epidermal growth factor receptor 2(HER2)and carbohydrate antigen 153(CA153)and the technical parameter of acoustic palpation tissue imaging quantification(VTIQ)in patients with breast cancer.Methods:A total of 80 female patients with breast cancer admitted to The Third People's Hospital of Hefei from May 2018 to May 2020 were selected,including 14 cases at WHO stage Ⅰ,22 cases at WHO stage Ⅱ,31 cases at WHO stage Ⅲ and 13 cases at WHO stage Ⅳ.Another 53 female patients with benign breast diseases who were treated during the same period were selected as controls.At first,all patients underwent routine ultrasound examination,and then they entered the ultrasound VTIQ imaging mode to obtain the mean value of shear wave velocity(SWV).An immunohistochemistry was used to detect HER2 expressions in breast tissues,and Roche E411 electrochemiluminescence immunoassay analyzer was used to detect serum CA153 levels of them.Pearson method was used to analyze the correlation between serum CA153 levels and SWV mean values in patients with breast cancer.Results:Compared with benign patients,the SWV mean value of VTIQ technical parameter,serum CA153 level and HRR2 positive expression rate in patients with breast cancer were significantly higher,and the difference was statistically significant(F=39.107,78.353,P<0.05),respectively.Compared with patients at stages Ⅰ + Ⅱ of breast cancer,the SWV mean value of VTIQ technical parameter,serum CA153 level and HRR2 positive expression rate of patients at stages Ⅲ and Ⅳ of breast cancer significantly increased(t=2.685,3.556,8.326,10.455,P<0.05),respectively.Compared with patients at stage Ⅲ of breast cancer,the SWV mean value of VTIQ technical parameters,serum CA153 level and HRR2 positive expression rate of patients at Ⅳ stage of breast cancer were significantly higher(t=4.632,8.659,P<0.05),respectively.Compared with the SWV mean value of patients with HER2 negative expression of breast cancer,that of patients with HER2 positive expression of breast cancer was significantly higher(x2=59.751,P<0.05).There was a positive correlation between serum CA153 levels and SWV mean values in patients with breast cancer(r=0.501,P<0.05).Conclusion:The SWV mean value of VTIQ parameters is closely related to the expression levels of biomarkers HER2 and CA153 in patients with breast cancer.

Efficacy of trastuzumab deruxtecan in treatment of metastatic breast cancer with overexpression or low expression of HER2 and the influencing factors of prognosis / 肿瘤研究与临床

Objective:To investigate the effect of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer (MBC) patients with different expression levels of human epidermal growth factor receptor 2 (HER2) and the influencing factors of prognosis.Methods:The retrospective case series analysis and cohort study were conducted. Clinical data of 20 MBC patients with different expression levels of HER2 treated with T-DXd at Xi'an International Medical Center Hospital from August 2021 to August 2023 were retrospectively collected to analyze the efficacy and safety of T-DXd. The Cox proportional hazards model was used for multivariate analysis of prognostic factors.Results:All 20 patients were female, with a median age [ M ( Q1, Q3)] of 49 years old (40 years old, 58 years old). Of the 20 cases, 12 had low expression of HER2 [immunohistochemistry HER2+, or immunohistochemistry ++ and fluorescence in situ hybridization (FISH)-negative], and 8 had overexpression of HER2 (immunohistochemistry HER2+++, or immunohistochemistry ++ and FISH-positive); median number of lines of treatment with T-DXd was 6 lines (3 lines, 7 lines); 14 patients had partial remission, 3 patients had stable disease, and 3 patients had disease progression, with an objective remission rate (ORR) of 70% (14/20) and a disease control rate of 85% (17/20). Eight patients with overexpression of HER2 had objective remission in 6 cases, and 12 patients with low expression of HER2 had objective remission in 8 cases, and the ORR difference between the two groups was not statistically significant ( P = 1.000). The main adverse reactions of the patients were nausea (14 cases), vomiting (12 cases), leukopenia (10 cases), elevated aspartate aminotransferase (10 cases), elevated alanine aminotransferase (9 cases), anemia (8 cases), fatigue (8 cases), alopecia (8 cases), neutropenia (6 cases), and thrombocytopenia (5 cases); ≥ grade 3 adverse reactions were bone marrow suppression and gastrointestinal reactions, all with an incidence of ≤10%. The median follow-up time was 7.1 months (1.9 months, 11.5 months). The median progression-free survival (PFS) time was 6.5 months (95% CI: 3.9-9.1 months), and the median PFS time of patients with overexpression of HER2 was longer than that of patients with low expression of HER2 [7.0 months (95% CI: 6.4- 7.6 months) vs. 4.0 months (95% CI: 1.7-6.3 months)], and the difference in PFS between the two groups was statistically significant ( P = 0.025). Multivariate Cox regression analysis showed that overexpression of HER2 was an independent protective factor for PFS in MBC patients treated with T-DXd ( HR = 0.265, 95% CI: 0.075-0.945, P = 0.041). Conclusions:MBC patients with overexpression or low expression of HER2 have a good therapeutic effect and safety profile when treated with T-DXd. The overexpression of HER2 may predict good PFS in MBC patients treated with T-DXd, and may serve as a biomarker for predicting PFS in such patients, but it may not affect the ORR.

Application and clinical progress of pyrotinib in breast cancer / 肿瘤研究与临床

Pyrotinib is a new irreversible epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) dual tyrosine kinase inhibitor, and it has shown excellent clinical efficacy in treatment of HER2-positive breast cancer patients. The combination of pyrotinib and capecitabine in the treatment of advanced breast cancer has been recognized at home and abroad. Further exploration of whether there are other antitumor agents that work well in combination with pyrotinib, and whether pyrotinib can enhance clinical benefit in patients with early-stage or middle-stage breast cancer, could develop additional potential of pyrotinib. This article reviews the progress related to pyrotinib in recent years.

Clinicopathological features and prognosis analysis of salivary duct carcinoma / 口腔疾病防治

Objective@#To summarize the clinicopathological characteristics and prognostic factors of salivary duct carcinoma (SDC) patients.@*Methods@#This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. The clinical data of 30 SDC patients who were admitted to the Fourth Hospital of Hebei Medical University from 2014 to 2022, including case records, pathological diagnoses, immunohistochemical indicators, treatment methods, follow-up data, and other data, were retrospectively analyzed. SPSS 26.0 software was used to process the data and construct relevant curves. The chi-square test was used to analyze the correlation between different immunohistochemical indices and the recurrence and metastasis of SDC, and a single factor was used to analyze clinical prognostic factors.@*Results@#Among the 30 SDC patients, the male-to-female ratio was 5∶1, with a median age of 61.5 years. Approximately 60% of cases occurred in the parotid gland, whereas the remainder occurred in the submaxillary gland, sublingual gland, or minor salivary gland. Among them, 19 patients were androgen receptor-positive, 23 patients were human epidermal growth factor receptor-2 positive, and 26 patients were Ki-67 positive. Postoperative follow-up was 18-94 months, with a median follow-up of 37 months. There were 13 cases of recurrence and 14 cases of distant metastasis. The 5-year overall survival rate was only 31.2%. The long-term survival of patients who underwent postoperative radiotherapy and chemoradiotherapy was better than that of patients who underwent surgery alone (P= 0.027). T stage and lymph node invasion were associated with prognosis and survival (P<0.05). There was a correlation between a Ki-67-positive cell count ≥ 40% and postoperative recurrence or metastasis (P = 0.025).@*Conclusion@#Radical surgery combined with postoperative radiotherapy and chemoradiotherapy is helpful for improving long-term overall survival, and tumor T stage and lymph node metastasis may be the main factors affecting the prognosis of patients with SDC. Patients with Ki-67-positive cell counts ≥ 40% are prone to postoperative recurrence or metastasis.

Clinical application and progression of monoclonal antibodies targeting HER2 extracellular domain Ⅳ in breast cancer / 中国药房

Human epidermal growth factor receptor 2 （HER2）-positive breast cancer is aggressive and prone to metastasis，and the applications of HER2 agents have improved the prognosis of patients with HER2-positive breast cancer. Among the marketed HER2 agents，macromolecular monoclonal antibodies that target the extracellular domain Ⅳ of HER2 were the cornerstone drugs of HER2-positive breast cancer，including trastuzumab，inetetamab，and margetuximab. Trastuzumab is available for the full-line treatment of breast cancer with sufficient proof of evidence-based medicine，sufficient practical experience and controllable safety. Inetetamab and trastuzumab have similar efficacy and controllable safety in HER2-positive metastatic breast cancer and neoadjuvant/ adjuvant therapy. Margetuximab focuses on patients carrying the CD16A-158F allele，and is an option of posterior line treatment for advanced breast cancer. It is necessary to select the most suitable drugs clinically according to the specific condition of the patient.

Expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/neu in gallbladder carcinoma in North Indian population

Background: Gallbladder carcinoma (GBC) although rare is most frequent malignant neoplasm of biliary tract system and sixth most common malignancy of digestive tract. GBC is more common in females and there are studies which show expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 neu (HER2/neu) in GBC suggesting possible molecules for targeted therapy, but results are inconsistent. Aims and Objectives: The aim of this study was to find out expression of ER, PR, and HER2/neu in GBC in North Indian population and their possible association with clinicopathological features. Materials and Methods: A total 59 resected cases of GBC diagnosed by histopathological examination were included in the study. Expression of ER, PR, and HER2/neu was accessed by immunohistochemistry method and correlated with various clinicopathological features. Results: ER expression was absent in all GBC cases. PR expression was present in only one case. Positive expression of HER2/neu was present in 13 (22%) cases, in which 12 cases were of conventional adenocarcinoma and one case was of papillary adenocarcinoma. Well and moderately differentiated tumor had significantly higher HER2/neu expression as compared to poorly differentiated tumors (P = 0.001). Pre-obese patients had significantly higher HER2/neu expression as compared to non-obese patients (P = 0.008). Conclusion: In our study, there was no expression of estrogen and PR in GBC in North Indian population. Although small in number, there is a subset of patients who overexpress HER2/neu receptor that may benefit from targeted therapy.

Characteristics and Research Progress of Traditional Chinese Medicine in Treatment of HER-2-Positive Breast Cancer： A Review / 中国实验方剂学杂志

Human epidermal growth factor receptor-2 （HER-2）-positive breast cancer has higher predilection to metastasize and invade other organs， leading to poor prognosis. The anti-HER-2 drugs， such as trastuzumab， pertuzumab， and trastuzumab emtansinehas， can remarkably prolong the disease free survival （DFS） of patients. However， frequent multidrug resistance， tumor recurrence and metastasis， and adverse reactions such as cardiotoxicity and gastrointestinal discomfort caused by adjuvant therapy are still challenges for the treatment of HER-2-positive breast cancer. The understanding of breast cancer in traditional Chinese medicine （TCM） has a long history. In thousands of years of inheritance and innovation， a standardized treatment system with TCM characteristics has been gradually formed， which shows unique advantages and significant curative effects in breast cancer treatment. The treatment principles of ''treatment based on syndrome differentiation''， ''treatment based on stages and types''， ''treatment according to individual conditions''， and ''treatment of different viscera and viscera based on the toxin and pathogen'' are closely related to the precise treatment concept. In view of the challenges in the treatment of HER-2-positive breast cancer， such as multidrug resistance， tumor recurrence and metastasis， cardiotoxicity， and gastrointestinal discomfort， this paper summarizes the characteristics of TCM in reversing the multidrug resistance， inhibiting tumor recurrence and metastasis， prolonging DFS， improving prognosis， reducing adverse reactions caused by adjuvant therapy， and improving the quality of life after breast cancer surgery according to the principles of reinforcing healthy Qi and eliminating pathogen， and treatment based on syndrome differentiation. This article is expected to serve as a reference for TCM treatment of HER-2 positive breast cancer.

Pathological Types,Expression of Mismatch Repair Protein,Human Epidermal Growth Factor Receptor 2,and Pan-TRK,and Eostein-Barr Virus Infection in Patients With Colorectal Cancer Resected in Tibet / 中国医学科学院学报

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.

Magnetic resonance differential analysis for different hormone receptor expression status in HER-2-positive breast cancer / 中南大学学报(医学版)

OBJECTIVES@#Currently, it is difficult to assess the expression status of hormone receptor (HR) in breast malignant tumors with human epidermal growth factor receptor 2 (HER-2)-positive in the early preoperative stage, and it is difficult to predict whether it is non-invasively. This study aims to explore the value of MRI on the different HR expression status (HR+/HR-) in HER-2 positive breast cancer.@*METHODS@#Thirty patients with HR+ HER-2-positive breast cancer (HR+ group) and 23 patients with HR-HER-2-positive breast cancer (HR- group) from the First Hospital of Hunan University of Traditional Chinese Medicine between January 7, 2015 and November 26, 2021 were selected as subjects, and all the patients were examined by MRI and all were confirmed by surgery or pathological biopsy puncture. The immunohistochemical staining results were used as the gold standard to analyze the basic clinical conditions, peri-lesion conditions and MRI sign characteristics in the 2 groups.@*RESULTS@#There were all significant differences in terms of mass margins, internal reinforcement features, and apparent diffusion coefficient (ADC) values between the HR+ group and the HR- group (all P<0.05). The logistic multivariate regression model showed that: when the lesion presented as a mass-type breast cancer on MRI, the internal enhancement features of the lesion were an independent predictor for differentiation in the 2 types of breast cancer [odds ratio (OR)=5.95, 95% CI: 1.223 to 28.951, P<0.05], and the mass margin (OR=0.386, 95% CI: 0.137 to 1.082, P>0.05) and ADC value (OR=0.234, 95% CI: 0.001 to 105.293, P>0.05) were not the independent predictors in distinguishing the 2 types of breast cancer.@*CONCLUSIONS@#Multiparametric MRI has good diagnostic value for HR expression status in HER-2-positive breast cancer. Combined logistic regression analysis to construct a predictive model may be helpful to the identical diagnosis.

Efficacy and safety of olaparib in adjuvant therapy of BRCA1/2 mutated HER2-negative breast cancer：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of olaparib in adjuvant therapy of breast cancer susceptibility gene （BRCA） 1/2 mutated human epidermal growth factor receptor 2 （HER2）-negative breast cancer， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from CNKI， VIP， Wanfang data， PubMed， ScienceDirect， the Cochrane Library and Embase databases， randomized controlled trials about adjuvant therapy of olaparib （trial group） versus adjuvant therapy of other drugs （control group） were collected. After literature screening and data extraction， meta-analysis， publication bias analysis and sensitivity analysis were performed by using RevMan5.4 software. RESULTS A total of 5 randomized controlled trials were included， with a total of 2 633 patients， including 1 495 cases in trial group and 1 174 cases in control group. Meta-analysis showed that in terms of efficacy， compared with control group， overall survival [HR＝1.02， 95%CI （1.01，1.03）， P＝0.000 8] and progression-free survival [HR＝1.78， 95%CI（1.46，2.17）， P＜0.000 01] were longer significantly in the trial group. In terms of safety， compared with the control group， the incidence of adverse drug reactions at any level in the trial group was higher [RR＝1.41， 95%CI （1.12， 1.78）， P＝0.004]， while there was no statistically significant difference in the incidence of adverse drug reactions above level 3 between the two groups [RR＝1.75， 95%CI （0.82， 3.74）， P＝0.15]. The results of publication bias indicated that the possibility of publication bias in this study was relatively low. The results of sensitivity analysis showed that the results obtained in this study were robust. CONCLUSIONS Compared with patients without adjuvant therapy of olaparib， adjuvant therapy of olaparib can prolong overall survival and progression-free survival of patients with BRCA1/2 mutated HER2-negative breast cancer，but the risk of adverse drug reactions is relatively high.

Effects of adjuvant trastuzumab on long-term survival of T1N0M0 stage human epidermal growth factor receptor 2 positive breast cancer: a real-world study / 中华肿瘤杂志

Objective: To investigate the prognosis impact of adjuvant trastuzumab treatment on human epidermal growth factor receptor 2 (HER-2) positive early breast cancer patients. Methods: A retrospective study was conducted, HER-2-positive T1N0M0 stage breast cancer patients who underwent surgery in the Affiliated Tumor Hospital of Xinjiang Medical University from January 2010 to December 2019 were divided into treatment group and control group according to whether they were treated with trastuzumab or not. Propensity score matching (PSM) was used to balance the confounding bias caused by differences in baseline characteristics between the two groups. Cox proportional hazards model was used to analyze the risk factors affecting disease-free survival (DFS). The Kaplan-Meier method was used to estimate the 3- and 5-year DFS and overall survival (OS) rates of the two groups before and after PSM. Results: There were 291 patients with HER-2 positive T1N0M0 stage breast cancer, including 21 cases in T1a (7.2%), 61 cases in T1b (21.0%), and 209 cases in T1c (71.8%). Before PSM, there were 132 cases in the treatment group and 159 cases in the control group, the 5-year DFS rate was 88.5%, and the 5-year OS rate was 91.5%. After PSM, there were 103 cases in the treatment group and 103 cases in the control group, the 5-year DFS rate was 86.0%, and the 5-year OS rate was 88.5%. Before PSM, there were significant differences in tumor size, histological grade, vascular invasion, Ki-67 index, postoperative chemotherapy or not and radiotherapy between the treatment group and the control group (P<0.05). After PSM, there were no significant difference in clinicopathological features between the treatment group and the control group (P>0.05). Multivariate analysis showed that histological grade (HR=2.927, 95 CI: 1.476, 5.805; P=0.002), vascular invasion (HR=3.410, 95 CI: 1.170, 9.940; P=0.025), menstrual status (HR=3.692, 95 CI: 1.021, 13.344, P=0.046), and chemotherapy (HR=0.238, 95 CI: 0.079, 0.720; P=0.011) were independent factors affecting DFS. After PSM, the 5-year DFS rate of the treatment group was 89.2%, while that of the control group was 83.5%(P=0.237). The 5-year OS rate of the treatment group was 96.1%, while that of the control group was 84.7%(P=0.036). Conclusion: Postoperative targeted therapy with trastuzumab can reduce the risk of recurrence and metastasis in patients with HER-2-positive T1N0M0 stage breast cancer.

Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers / 中华肿瘤杂志

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.

Consensus on the clinical use of CDK4/6 inhibitors for the treatment of hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer (2023 edition) / 中华肿瘤杂志

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have led transformative breakthrough of clinical therapy for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER-2)-negative breast cancer patients. CDK4/6 inhibitors that have been marketed in China include Ribociclib, Palbociclib, Abemaciclib and Dalpiciclib. For HR-positive HER-2-negative locally advanced and metastatic breast cancer, CDK4/6 inhibitors combined with endocrine therapy have become standard regimen, which can prolong the survival of patients. In the adjuvant treatment stage of early breast cancer, CDK4/6 inhibitors have also achieved positive results and been approved for indications. At present, CDK4/6 inhibitors have been widely used in clinical practice in China. In order to further improve the standardized application of CDK4/6 inhibitors in China, the Breast Cancer Expert Committee of the National Center for Cancer Quality Control and the Professional Committee of Clinical Research of Cancer Drugs of the Chinese Anti-Cancer Association organized the related expert to update the consensus based on the "CDK4/6 inhibitor consensus on clinical application of in the treatment of hormone receptor positive human epidermal growth factor receptor 2 negative advanced breast cancer (2021 edition)" . The updated consensus systematically introduces the pharmacological characteristics, drug monitoring and adverse event management, etc., of CDK4/6 inhibitors to promote the accuracy of clinical decision-making with the ultimate goal to prolong the overall survival of patients and improve the quality of life.

Efficacy of lapatinib combined with trastuzumab on patients with HER2-positive breast cancer and analysis of survival prognosis / 临床外科杂志

Objective To explore the efficacy of lapatinib combined with trastuzumab in the treatment of patients with human epidermal growth factor receptor-2(HER2)-positive breast cancer and its effects on survival prognosis.Methods 86 patients with HER2-positive breast cancer who were treated with neoadjuvant chemotherapy from April 2016 to June 2018 were selected as the research subjects,and they were divided into observation group(lapatinib combined with trastuzumab treatment)and control group(trastuzumab treatment)by means of the random number table method,with 43 cases in each group.The therapeutic efficacy of the two groups was compared,and the changes in levels of vascular endothelial growth factor,inflammatory factors and apoptotic factors were recorded before and after treatment.All patients were followed up for 3 years or until their death,and the cumulative survival rate was compared between the two groups,and the occurrence of adverse events during treatment were counted.Results There were no significant differences in objective response rate(ORR)and disease control rate(DCR)between observation group and control group(72.09％vs 58.14％,86.07％vs 74.42％,P＞0.05).After treatment,the levels of vascular endothelial growth factor A(VEGFA),vascular endothelial growth factor B(VEGFB),vascular endothelial growth factor C(VEGFC),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1 β),interleukin-6(IL-6)and interleukin-8(IL-8)in observation group were lower than those in control group,and the expression levels of decoy receptor 3(DcR3)and cyclooxygenase-2(COX-2)after treatment were also lower than those in control group(P＜0.05).The 3-year survival rates in observation group and control group were 46.51％(20/43)and 30.23％(13/43),and the median survival times were 34.5 months and 26.7 months(P＞0.05).There were no significant differences between the two groups in terms of incidence rates of adverse events(P＞0.05).Conclusion Lapatinib combined with trastuzumab in the treatment of patients with HER2-positive breast cancer can reduce the levels of vascular endothelial factors and inflammatory factors and inhibit the releases of apoptotic factors,but has little effect on the 3-year survival rate of patients.

The impact of HER2 and C-reactive protein/albumin ratio on the long-term survival of gastric cancer patients after surgery / 中国医师杂志

Objective:To investigate the impact of human epidermal growth factor receptor 2 (HER2) and C-reactive protein/albumin ratio (CAR) on the long-term survival of gastric cancer patients after surgery.Methods:A retrospective analysis was conducted on 136 gastric cancer patients admitted to Lishui Central Hospital from January 2015 to December 2017, who underwent radical surgery and were followed up for 5 years. Patients were divided into HER2 positive and HER2 negative groups based on HER2 immunohistochemical results, and into high CAR and low CAR groups based on the CAR mean value. The relationship between HER2 and CAR with clinicopathological characteristics of gastric cancer patients was analyzed. The postoperative tumor-free survival rate and overall survival rate were compared between the two groups of patients (HER2 positive group and HER2 negative group, as well as high CAR group and low CAR group). Cox regression analysis was used to identify independent prognostic factors for postoperative tumor recurrence, metastasis, and death in gastric cancer patients.Results:The proportion of HER2 positive patients with large tumor size, low differentiation, T 3-4 tumor invasion depth, lymph node metastasis, and vascular invasion was significantly higher than that of HER2 negative patients (all P<0.05). The proportion of high CAR patients with large tumor size, low differentiation, T 3-4 tumor invasion depth, lymph node metastasis, and vascular invasion was significantly higher than that of low CAR patients (all P<0.05). Kaplan-Meier survival analysis showed that HER2 negative patients had significantly higher 1-year, 3-year, and 5-year cumulative tumor-free survival rate and overall survival rate than HER2 positive patients, while low CAR patients had significantly higher 1-year, 3-year, and 5-year cumulative tumor-free survival rate and overall survival rate than high CAR patients (all P<0.05). Multivariate Cox regression analysis identified T 3-4 tumor invasion depth, lymph node metastasis, HER2 positivity, and high CAR expression as independent prognostic factors for postoperative tumor recurrence, metastasis, and death in gastric cancer patients (all P<0.05). HER2 positive gastric cancer patients had a 1.895-fold higher risk of postoperative tumor recurrence and metastasis than HER2 negative patients ( HR: 1.895, 95% CI: 1.245-4.229, P=0.034), while high CAR gastric cancer patients had a 1.769-fold higher risk of postoperative tumor recurrence and metastasis than low CAR patients ( HR: 1.769, 95% CI: 1.433-3.959, P=0.039). HER2 positive gastric cancer patients had a 2.145-fold higher risk of postoperative death than HER2 negative patients ( HR: 2.145, 95% CI: 1.378-4.589, P=0.028), while high CAR gastric cancer patients had a 1.926-fold higher risk of postoperative death than low CAR patients ( HR: 1.926, 95% CI: 1.564-3.853, P=0.025). Conclusions:HER2 and CAR are independent prognostic factors for postoperative tumor recurrence, metastasis, and death in gastric cancer patients. Gastric cancer patients with HER2 positivity and high CAR have a higher risk of postoperative tumor recurrence, metastasis, and death. This study has some limitations due to its small sample size and single-center design, which may introduce some bias. Future multicenter and large-scale studies are needed to confirm the results of this study.

Efficacy of postmastectomy radiotherapy for HER2-positive T 1-2N 1M 0 breast cancer / 中华放射医学与防护杂志

Objective:To investigate the efficacy of postmastectomy radiotherapy (PMRT) for human epidermal growth factor receptor 2 (HER2)-positive T 1-2N 1M 0 breast cancer in the context of HER2-targeted therapy. Methods:This study collected the clinical data of 105 female patients with HER2-positive T 1-2N 1M 0 breast cancer who underwent modified radical mastectomy in the First Affiliated Hospital of Bengbu Medical College from January 2013 to December 2019. Then, the clinical outcomes of these patients were observed, and the prognostic factors and the efficacy of PMRT were analyzed. Results:The median follow-up time was 50 months (ranging from 14 to 107 months), and the 5-year overall survival (OS), local-regional recurrence-free survival(LRFS), and disease-free survival (DFS) were 81.6%, 91.9%, and 76.2%, respectively. The multivariate analysis indicated that independent prognostic factors for OS and DFS include the age, pathologic grade, and tumor size; the independent risk factors for LRFS include positive lymph node ratio (LNR) and hormone receptor (HR) status; and the independent prognostic factor for DFS was PMRT (HR: 2.85, 95% CI: 1.10-8.80, P < 0.05). The subgroup analysis suggested that PMRT significantly improved the OS of various high-risk subgroups ( χ2=4.01-9.18, P < 0.05). However, the further stratified analysis indicated that PMRT only increased the OS of the patients who did not receive HER2-targeted therapy in various high-risk subgroups ( χ2=4.50-6.70, P < 0.05), while there was no statistical difference before and after PMRT for the individuals who received targeted treatment ( P > 0.05). Conclusions:PMRT is an independent prognostic factor for the DFS of patients with HER2-positive T 1-2N 1M 0 breast cancer who underwent modified radical mastectomy. PMRT can improve the OS of high-risk patients with ages < 45 years old, pathologic grade Ⅲ, tumor diameter ≥ 3 cm, LNR > 10%, and HR (-) who received no HER2-targeted therapy. However, the efficacy may be compromised to some extent in the context of the application of HER2-targeted therapy.

The research advances and the clinical value of antibody-drug conjugate from molecular subtyping of breast cancer in the era of"precision medicine" / 中国癌症杂志

The incidence of breast cancer currently ranks first among malignant tumors in women.Breast cancer exhibits high heterogeneity and can be classified into four molecular subtypes:luminal A,luminal B,human epidermal growth factor receptor 2(HER2)overexpression and triple-negative.However,previous molecular subtype classifications have limited treatment options for patients with HER2 low expression.In recent years,with the rapid development of antibody-drug conjugates(ADCs),new treatment options have emerged for breast cancer patients with HER2 low expression.This has also led to updates in the criteria for determining HER2 expression status in both domestic and international guidelines,based on immunohistochemistry(IHC)and in situ hybridization(ISH)testing,categorizing HER2 expression as HER2-positive(IHC 3+ or IHC 2+/ISH+),HER2 low expression(IHC 1+ or IHC 2+/ISH-),and HER2-negative(IHC 0).ADCs are immunotherapeutics composed of a linker that conjugates a monoclonal antibody with a cytotoxic payload.In the field of breast cancer,several large clinical trials have demonstrated clinical benefits of ADCs targeting HER2,such as trastuzumab emtansine(T-DM1),trastuzumab deruxtecan(T-DXd)and sacituzumab govitecan targeting trophoblast cell surface antigen 2(TROP2),in various molecular subtypes of breast cancer.With the phaseⅢ DESTINY-Breast03 trial and others,T-DXd has been found to have superior efficacy compared to T-DM1 in advanced HER2-positive breast cancer patients(approximately two times higher complete response rate,and four times longer median progression-free survival).T-DXd has now replaced T-DM1 as the recommended second-line therapy for HER2-positive breast cancer and as a second-line treatment option after local treatment for brain metastasis.The phase Ⅲ DESTINY-Breast04 trial confirmed that breast cancer patients with HER2 low expression can also benefit from T-DXd,further reshaping the treatment landscape for advanced breast cancer and supporting the need to redefine molecular subtypes of HER2-negative breast cancer.The phase Ⅲ ASCENT trial demonstrated that sacituzumab govitecan significantly improved survival and quality of life in triple-negative breast cancer(TNBC)patients,and the phase Ⅱ NeoSTAR study suggested its potential as neoadjuvant therapy in TNBC.Based on evidence,T-DM1,T-DXd and sacituzumab govitecan have been approved for marketing in both foreign and Chinese markets.Other ADC drugs,such as HER3-DXd,Dato-DXd and China-developed RC48,are also undergoing extensive clinical trials in the field of breast cancer and other tumors.Furthermore,there are several other ADCs targeting different molecular targets in active development.This article aimed to review the new advances related to ADCs therapy for breast cancer patients with different molecular subtypes and discuss the clinical application value of ADCs in breast cancer.

Expressions of survivin, p53 and human epidermal growth factor receptor 2 in breast cancer tissues and their prognostic value / 肿瘤研究与临床

Objective:To investigate the expressions of apoptosis-related factors survivin, p53 and human epidermal growth factor receptor 2 (HER2) in breast cancer tissues and their prognostic value.Methods:A total of 131 patients undergoing radical mastectomy for breast cancer who were admitted to Tangshan Maternal and Child Health Care Hospital from February 2015 to January 2019 were selected as the research subjects. During the operation, the cancer tissues and adjacent tissues (normal tissues >3 cm from the tumor margin) were collected from the patients. Expressions of survivin, p53 and HER2 in cancer tissues and adjacent tissues of patients were detected by using immunohistochemistry. The prognoses of patients were recorded after the follow-up for 3 years; the recurrence, metastasis and death treated as the poor prognosis, the rest prognoses of patients were treated as the good prognosis group. The difference of clinicopathological characteristics between the poor prognosis group and the good prognosis group was compared. Multivariate logistic regression was used to analyze risk factors for prognosis of breast cancer patients. The result of prognosis of breast cancer was taken as the golden standard. The receiver operating characteristic (ROC) curve was used to analyze the value of survivin pasitive, p53 pasitive, HER2 pasitive alone, the combination of both and the combination of the there in the judgement of poor prognosis of breast cancer.Results:The positive expression rates of survivin [49.6% (65/131) vs. 7.6% (10/131)], p53 [60.3% (79/131) vs. 13.0% (17/131)] and HER2 [79.4% (104/131) vs. 16.8% (22/131)] in cancer tissues were higher than those in adjacent tissues (all P<0.001). A total of 131 breast cancer patients were followed up for 3 years without any loss of follow-up, and the follow-up rate was 100%. Within the follow-up for 3 years, there were 15 (11.5%) cases of recurrence, 8 (6.1%) cases of metastasis, and 10 (7.6%) cases of death, the incidence of poor prognosis was 25.2% (33/131); and the remaining 98 cases had good prognosis. The proportions of patients with TNM stage Ⅲ, lymph node metastasis, poorly differentiated histology, tumor diameter ≥3 cm, survivin, p53, and HER2 positive expressions in the poor prognosis group were higher than those in the good prognosis group (all P<0.05). Multivariate logistic regression analysis showed that TNM stage Ⅲ [ OR = 5.323 (95% CI 2.190-12.936)], lymph node metastasis [ OR = 4.773 (95% CI 1.964-11.600)], tumor diameter ≥3 cm [ OR = 3.582(95% CI 1.474-8.706)], positive survivin [ OR = 2.740 (95% CI 1.127-6.659)], positive p53 [ OR = 3.271 (95% CI 1.346-7.949)], and positive HER2 [ OR = 3.873 (95% CI 1.594-9.412)] were independent risk factors for prognosis of breast cancer (all P<0.001). The ROC curve results showed that the area under the curve (AUC) values of survivin positive, p53 positive,HER2 positive, and the combination of any two were more than 0.80 (all P<0.001); the AUC of the combination of the three was 0.944 (95% CI 0.890-0.977) ( P<0.001). Conclusions:The expressions of survivin, p53, and HER2 are highly expressed in breast cancer tissues. The expressions of the three can be used to judge the prognosis of breast cancer patients, and the combination of the three has a higher judgement value.