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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Anciano de 80 o más Años , Adenocarcinoma , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/patología , Reparación de la Incompatibilidad de ADN , Proteínas de Unión al ADN/genética , Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4/metabolismo , Hibridación Fluorescente in Situ , Metástasis Linfática , TibetRESUMEN
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.
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Humanos , Femenino , Neoplasias de la Mama/cirugía , Imagen por Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Mama , Espectroscopía de Resonancia Magnética , Estudios RetrospectivosRESUMEN
OBJECTIVE@#There is an increasing interest in human epidermal growth factor receptor 2 (HER2) low expression breast cancer with the result of novel anti-HER2 antibody-drug conjugates for breast cancer. HER2 low expression breast cancer is expected to become a new type of breast cancer. This study analyzed and compared the clinicopathological features and survival data of breast cancer with HER2 low expression group [immunohistochemistry (IHC) 1+ or IHC 2+, and fluorescence in situ hybridization (FISH) negative] and HER2 zero expression group (IHC 0), in order to explore the difference in clinical biology of HER2 low expression breast cancers.@*METHODS@#Among 1 250 female patients with primary non-metastatic breast cancer admitted to the Breast Disease Center of Peking University First Hospital from January 2014 to December 2017, 969 cases were HER2 negative (IHC 0, 1+, 2+, and FISH was not amplified). The clinicopathologic features and prognosis of the patients with HER2 low expression (IHC 1+ or 2+, and unamplified by FISH) and HER2 zero expression (IHC 0) were analyzed. Disease free survival (DFS) and overall survival (OS) were evaluated, survival rates were calculated by Kaplan-Meier curve, and survival differences were compared by Log-rank test. Cox regression analysis of univariate and multivariate prognostic factors. Bilateral test was used, and P < 0.05 was considered statistically significant.@*RESULTS@#In the 969 patients with HER2 negative breast cancer, 606 had HER2 low expression (62.54%) and 363 had HER2 zero expression (37.46%). Compared with breast cancer with HER2 zero expression, those with HER2 low expression had higher N stage (P=0.001) and TNM stage (P=0.044), the proportion of non-specific histological types was higher (82.7% vs. 79.1%, P=0.009), the histological grade was higher (P=0.048), and the positive rate of hormone receptor was higher (83.2% vs. 75.2%, P=0.003). The percentage of Ki-67 value index >30% was lower (30.4% vs. 36.6%, P=0.044). There was no significant difference in DFS and OS between the two groups (P>0.05). In the 969 cases, 777 were hormone receptor positive and 192 were hormone receptor negative (triple negative cancer). Among the 777 cases with hormone receptor positive, 504 (64.9%) were HER2 low expression, and 273 (35.1%) were HER2 zero expression. Compared with breast cancer with HER2 zero expression group, the HER2 low expression group had a younger age (P=0.016), a higher proportion of premenopausal patients (P=0.029), more lymph node involvement (P=0.002), and a higher total TNM stage (P=0.031), and less frequent histological types of lobular and mucinous carcinoma (3.6% vs. 7.3%, 4.8% vs. 10.6%, P=0.001). There was no difference in DFS and OS between HER2 low expression and zero expression (P>0.05). Among 192 patients with hormone receptor negative, there were 102 cases (53.1%) with HER2 low expression and 90 cases (46.9%) with HER2 zero expression. Compared with the HER2 zero expression groups, HER2 low expression group was older (P=0.001), the proportion of premenopausal patients was low (P=0.029), the histological grade was lower (P < 0.001), the Ki-67 value index was lower (P < 0.001), and androgen receptor positive rate was higher (58.8% vs. 34.4%, P < 0.001). DFS was better than HER2 zero expression group (P=0.038), but there was no difference in OS between the two groups (P>0.05).@*CONCLUSION@#HER2 low expression breast cancer accounts for about half of all breast cancers, and the incidence is much higher than that of HER2 positive breast cancer. Its clinicopathologic features are heterogeneous, and the status of hormone receptor expression has an impact on the clinical biology of this group.
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Humanos , Femenino , Neoplasias de la Mama , Antígeno Ki-67 , Hibridación Fluorescente in Situ , Pronóstico , HormonasRESUMEN
Human epidermal growth factor receptor 2 (HER2) -positive breast cancer is prone to metastasis and has a poor prognosis. In the context of the booming development of anti-HER2 targeted therapy, HER2-positive breast cancer has reduced recurrence and metastasis and improved prognosis. However, there are still some HER2-positive breast cancer patients who cannot benefit from anti-HER2-targeted therapy and continue to develop recurrent metastasis. Neoadjuvant therapy, surgical treatment, and the full range of adjuvant and palliative therapies enable HER2-positive breast cancer to benefit from them. Scholars from home and abroad have explored the treatment of HER2-positive breast cancer and have achieved some results. In this article, we review the current status and development of HER2-positive breast cancer treatment.
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Objective:To investigate the risk factors of non-alcoholic fatty liver disease (NAFLD) in patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer (HR+/HER2-BC) and the impact of NAFLD on the survival of patients.Methods:54 HR+BC patients were enrolled in this study. The liver fat accumulation was examined by magnetic resonance imaging (MRI). The patients were divided into two groups: non-NAFLD and NAFLD. Student's t test or Fisher's test was used to analyze the clinical indicators of the two groups. Logistic univariate and multivariate tests were used to analyze the clinical risk factors related to NAFLD. Receiver operating characteristic curve (ROC curve) was used to further analyze the sensitivity of clinical risk factors to predict the diagnosis of NAFLD. The Disease-free survival (DFS) and Overall survival (OS) of the two groups were analyzed by Log-rank (Mantel-Cox) test. Results:There were 22 NAFLD patients and 32 non-NAFLD patients diagnosed by MRI. Student's t test or Fisher's test showed that BMI, waist circumference, AST, ALT, GGT, TG, LDL and HDL were statistically different between the two groups (all P<0.05). Logistic univariate and multivariate analysis showed that AST ( OR=1.05, 95% CI: 1.02-1.10, P=0.007), GGT ( OR=1.04, 95% CI: 1.01-1.09, P=0.038), TG ( OR=1.03, 95% CI: 1.01-1.06, P=0.011) and HDL ( OR=1.06, 95% CI: 1.01-1.12, P=0.037) were the risk factors associated with NAFLD. ROC curve analysis showed that the combination of AST, GGT, TG and HDL had high sensitivity in predicting NAFLD (AUC=0.869, P<0.05). There was no difference in DFS ( HR=1.830, 95% CI: 0.983-3.409, P=0.057) or OS ( HR=2.482, 95% CI: 0.761-8.093, P=0.132) between the two groups. Conclusion:AST, GGT, TG and HDL are the independent risk factors for NAFLD in HR+BC patients during treatment, but concurrent NAFLD has no significant effect on DFS or OS.
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Objective:To investigate the diagnostic value of dynamic contrast enhanced MRI (DCE-MRI) quantitative parameters for preoperative staging of gastric cancer and its relationship with prognostic factors.Methods:The clinical data of 98 patients with gastric cancer from March 2021 to March 2022 in Guangyuan First People′s Hospital were retrospectively analyzed. All patients underwent DCE-MRI examination, MRI features were observed, and the DCE-MRI quantitative parameters were recorded, including the transport constant (K trans), volume fraction (V e) and rate constant (K ep). The expression levels of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) in gastric cancer tissue were detected by immunohistochemistry methods. The correlation between DCE-MRI quantitative parameters and T stage, HER2, EGFR of gastric cancer was analyzed by Spearman method; the receiver operating characteristic (ROC) curve was used to evaluate the diagnosis value of DCE-MRI quantitative parameters in T staging of gastric cancer. Results:Among 98 patients with gastric cancer, T 1 to T 2 staging was in 50 cases, T 3 to T 4 staging was in 48 cases; HER2 positive expression in gastric cancer tissue was in 35 cases, negative expression was in 63 cases; EGFR positive expression in gastric cancer tissue was in 43 cases, negative expression was in 55 cases. The K trans and V e in patients with T 3 to T 4 staging were significantly higher than those in patients with T 1 to T 2 staging: (0.25 ± 0.04) min -1 vs. (0.19 ± 0.03) min -1 and 0.45 ± 0.11 vs. 0.39 ± 0.09, and there were statistical differences ( P<0.01); there was no statistical difference in K ep between the two ( P>0.05). The K trans and V e in patients with HER2 positive expression were significantly higher than those in patients with HER2 negative expression: (0.27 ± 0.06) min -1 vs. (0.19 ± 0.03) min -1 and 0.49 ± 0.13 vs. 0.38 ± 0.08, and there were statistical differences ( P<0.01); there was no statistical difference in K ep between the two ( P>0.05). The K trans and V e in patients with EGFR positive expression were significantly higher than those in patients with EGFR negative expression: (0.28 ± 0.07) min -1 vs. (0.17 ± 0.04) min -1 and 0.50 ± 0.14 vs. 0.36 ± 0.08, and there were statistical differences ( P<0.01); there was no statistical difference in K ep between the two ( P>0.05). Spearman analysis result showed that the K trans was positively correlated with gastric cancer T stage, and the expression of HER2, EGFR in gastric cancer tissue ( r = 0.539, 0.612 and 0.640; P<0.01), the V e was positively correlated with gastric cancer T stage, and the expression of HER2, EGFR in gastric cancer tissue ( r = 0.462, 0.551 and 0.583; P<0.01), while there was no correlated between K ep and gastric cancer T stage and the expression of HER2, EGFR in gastric cancer tissue ( P>0.05). ROC curve analysis result showed that the area under the curve of K trans combined with V e in diagnosis the T 3 to T 4 staging of gastric cancer was 0.929, with a specificity of 81.25% and a specificity of 92.00%. Conclusions:The DCE-MRI quantitative parameters K trans and V e have certain value in the diagnosis of gastric cancer T staging, and they are closely related to the expression of prognostic factors HER2 and EGFR.
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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.
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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.
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Humanos , Femenino , Neoplasias de la Mama/patología , Calidad de Vida , Consenso , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Receptor ErbB-2/metabolismo , Inhibidores de Proteínas Quinasas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quinasa 4 Dependiente de la Ciclina/metabolismoRESUMEN
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.
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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.
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OBJECTIVE To analyze the research status， hotspot and development trend of tyrosine kinase inhibitors （TKIs） in the treatment of human epidermal growth factor receptor 2 （HER2） positive breast cancer. METHODS The literature related to TKIs in the treatment of HER2 positive breast cancer were searched from the Web of Science core collection database； the author， country/region， institution， subject field， journal and keywords was visualized by CiteSpace 6.1.R3 software. RESULTS A total of 732 pieces of literature were included， and the number of literature published showed an increasing trend year by year. The number of literature published in the United States was the largest （center degree 0.10）， and the number of literature published in China ranked second （center degree 0.05）. The most published and cited authors were Crown from St. Vincent’s University Hospital in Australia and Slamon from University of California， Los Angeles in the United States； the institution with the highest number of literature was the University of Texas MD Anderson Cancer Center， and the journal with the highest number of literature was the Journal of Clinical Oncology. The research mainly focused on five aspects： HER2 positive breast cancer treatment drugs， TKIs receptor， TKIs mechanism of action， HER2 positive breast cancer brain metastasis， and TKIs clinical trials. The main frontier areas and development trends were the combination of TKIs with other drugs or therapies to enhance targeting and reduce toxic side effects. CONCLUSIONS The study of TKIs in the treatment of HER2 positive breast cancer has attracted the attention of scholars at home and abroad. Chinese scholars and research teams need to strengthen cooperation and communication in the future， and cooperation with other countries should be strengthened in terms of the efficacy and safety of TKIs alone and combined with other drugs in the treatment of HER2 positive breast cancer.
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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.