Strategy and Status of Neoadjuvant Therapy for HER2-positive Breast Cancer / 肿瘤防治研究

Neoadjuvant therapy is a preoperative systemic treatment for patients with breast cancer. This therapy has greatly improved the clinical outcomes of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which is associated with poor prognosis. Currently, dual anti-HER2 antibodies, including trastuzumab and pertuzumab, combined with non-anthracycline chemotherapy is one of the standard regimens to achieve high pathologic complete response rate and satisfactory efficacy. The combination of trastuzumab with tyrosine kinase inhibitors, antibody-drug conjugate drugs, or immunotherapy combined with target therapy, under the indications of reasonable biomarkers, is effective for HER2-positive breast cancer. In this article, we briefly reviewed neoadjuvant therapy in the dual-targeting therapy era and discussed its future perspectives.

Efficacy and safety of tyrosine kinase inhibitors in the treatment of HER2-positive breast cancer：a meta-analysis / 中国药房

OBJECTIVE To evaluate the efficacy and safety of tyrosine kinase inhibitors （TKI） in the treatment of HER2- positive breast cancer in order to provide evidence-based evidence for clinical medication. METHODS Retrieved from CNKI， Wanfang database， VIP， PubMed， Cochrane Library， Embase and Web of Science， randomized controlled trial （RCT） about TKI （trial group） versus drugs excluding TKI （control group） in the treatment of HER2-positive breast cancer were collected from the establishment of the database to April 2023. Meta-analysis and sensitivity analysis were performed by using RevMan 5.4.1 and Stata 17 software. RESULTS Total of 24 RCT studies were included， involving 15 538 HER2-positive breast cancer patients. The meta- analysis results showed that compared with the control group， the progression-free survival （PFS） [HR＝0.91， 95%CI （0.80， 1.02）， P＝0.12]， overall survival （OS） [HR＝0.95， 95%CI （0.89， 1.01）， P＝0.11]， objective response rate （ORR） [OR＝1.21， 95%CI （0.86， 1.69）， P＝0.27]， and pathological complete response rate （pCR） [OR＝1.44， 95%CI （0.91， 2.27）， P＝0.12] had no statistically significant difference in the trial group； among the 3/4 grade ADRs， the trial group had a higher incidence of anemia [OR＝1.77， 95%CI （1.16，2.70）， P＝0.008]， rash [OR＝11.26， 95%CI （7.32，17.31）， P＜0.000 01]， paronychia [OR＝8.67， 95%CI（1.62，46.53）， P＝0.01]， diarrhea [OR＝10.17， 95%CI（5.03，20.58）， P＜0.000 01]， oral mucositis inflammation [OR＝ 9.34， 95%CI （3.13， 27.83）， P＜0.000 1]， elevated aspartate aminotransferase [OR＝2.09， 95%CI （1.13，3.84）， P＝0.02]， and hypokalemia [OR＝2.37， 95%CI （1.31，4.30）， P＝0.005] than that of the control group. Subgroup analysis results showed that compared with the placebo group， TKI could improve OS and ORR （P＜0.05）， while compared with trastuzumab， TKI had no advantage in PFS， OS， ORR， and pCR， and TKI combined with trastuzumab could significantly improve PFS， OS， ORR， and pCR compared with the trastuzumab group （P＜ 0.05）. Sensitivity analysis suggested that the results were relatively robust and the risk of publication bias was low. CONCLUSIONS Compared with trastuzumab， TKI has no advantages in PFS， OS， ORR and pCR in the treatment of HER2- positive breast cancer， but TKI combined with trastuzumab can significantly improve PFS， OS， ORR and pCR； TKI can increase the risk of grade 3/4 anemia， rash， paronychia， diarrhea， oral mucositis， elevated aspartate aminotransferase， and hypokalemia.

Cost-utility analysis of trastuzumab deruxtecan versus trastuzumab emtansine in the second-line treatment for HER2-positive metastatic breast cancer / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of trastuzumab deruxtecan（T-DXd） versus trastuzumab emtansine （T-DM1） in the second-line treatment of HER2-positive metastatic breast cancer， and to provide a basis for the selection of clinical medication regimen and medical and health decisions. METHODS Based on the clinical trial DESTINY-Breast03， a partitioned survival model was constructed， with a cycle of 3 weeks as the simulation of patients’ lifetime. The incremental cost-effectiveness ratio （ICER） was calculated by using quality-adjusted life years （QALY） as output indicators， and sensitivity analysis was used to verify the robustness of the basic analysis results； the cost-effectiveness of the second-line treatment for HER2-positive metastatic breast cancer was compared between T-DXd and T-DM1. RESULTS Under the premise of taking 3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay threshold （257 094 yuan/QALY）， the T-DXd group also needed to pay more cost compared with T-DM1 group while obtaining incremental utility （0.69 QALYs）， and the ICER value was 1 850 478.40 yuan/QALY. The results of univariate sensitivity analysis showed that progression-free survival state utility value， T-DXd price， cost discount rate were factors that had a great influence on ICER value， but these parameters could not flip the basic analysis results within a reasonable range. In the probability sensitivity analysis， when the threshold of willingness-to-pay rose to 1 500 400 yuan/QALY， the probability of economic activity was 50% in the T-DXd regimen. The results of the scenario analysis also verified the robustness of the original research results. CONCLUSIONS Under the premise of 3 times China’s per capita GDP as the WTP threshold， compared with T-DM1， T-DXd is not cost-effective in the second-line treatment of HER2-positive metastatic breast cancer.

Construction of a column-line graph for predicting the probability of survival in early-stage elderly HER2-positive breast cancer based on the SEER database / 中国临床药理学与治疗学

AIM: To construct column-line plots to predict survival in elderly patients with early-stage HER2-positive breast cancer using the Surveillance, Epidemiology and End Results (SEER) database. METHODS: 5 220 (based on the era of single-targeted therapy) and 1 176 (based on the era of dual-targeted therapy) patients screened in the SEER database were randomized into a training group and an internal validation group. COX proportional risk regression was used to screen survival-related predictors and build a column-line graphical model, and the accuracy and utility of the model were tested using the consistency index (C-index), calibration curves, and time-dependent ROC curves. Patients receiving chemotherapy and non-chemotherapy were statistically paired using two-group propensity score matching, and subgroup analyses were performed on the screened variables. RESULTS: The single-targeted therapy era line graph was constructed from seven variables: age, marital status, T-stage, N-stage, surgery, chemotherapy, and radiotherapy. The dual-targeted therapy era line graph was constructed from five variables: age, AJCC staging, surgery, chemotherapy, and radiotherapy. The results of the subgroup analysis showed that older HER2-positive breast cancer patients who received chemotherapy had better OS. CONCLUSION: Based on the SEER database, an accurate column-line graph predicting survival in elderly patients with early-stage HER2-positive breast cancer was established and validated. This study suggests that chemotherapy increases survival benefit in elderly patients.

Molecular characterization and potential therapeutic roles of miR125a in HER-2 positive gastric cancer

Introduction: miR-125a-3p could have a role in gastric cancer by targeting HER2. This study aimed to investigate the expression pattern of miR-125a-3p, identify the expression level of its target gene in gastric carcinoma, and test its effect in HER-2 positive gastric carcinoma cells. Materials and Methods: The levels of miR-125a-3p in both cancer and noncancer tissues were measured by using Quantitative real-time polymerase chain in 70 gastric carcinomas. Immunohistochemical study was used to measure the expression of HER2 protein in these carcinomas. In addition, the level of expression of this miRNA is correlated to different pathological and clinical parameters. The effects of miR-125a-3p alone and in combination with 5-FU (fluorouracil) on the growth of HER2 positive (NUGC4) and HER2 negative (ECC10) gastric carcinoma cells were also analyzed by in vitro studies. Results: Most gastric cancer tissues samples showed downregulation of miR-125a-3p (84%) when compared to their noncancer tissues. Significant correlations of downregulation of miR-125a-3p with cancer recurrence and pathological staging of gastric carcinoma (P = 0. 02 and 0.02, respectively) were noted. HER2 protein expression correlated significantly and inversely with miR-125a-3p expression (P < 0.05). A reduction in cell growth rate was noted significantly in miR-125a-3p transfected gastric carcinoma cells when 5-FU was added to them in comparison to other control cells (P < 0.01). When both gastric carcinoma cell lines were transfected with miR-125a-3p, a significantly higher growth inhibition percentage in HER2 positive (NUGC4) cell line was seen in comparison to the HER2 negative (ECC10) cells (P < 0.01). Conclusion: miR-125a-3p plays a significant role in the pathogenesis of gastric carcinoma. Therapeutic transfection of miR-125a-3p in HER2 positive gastric cancer cells resulted in reduced cell proliferation and potentiate the effect of 5-FU.

Cáncer de mama Her2-positivo: Terapias sistémicas actuales y experiencia local

El cáncer de mama (CM) es la primera causa de muerte por cáncer en mujeres tanto a nivel mundial como en Chile. Basados en características clínicas, histológicas y moleculares, múltiples estudios han identificado cuatro subtipos básicos de CM, los cuales están asociados a estrategias de tratamiento específicas y diferenciadas. El CM HER2-positivo representa un 15%-25% de todas las neoplasias mamarias y se caracteriza por su agresividad, recurrencia temprana y mayor tendencia a presentar compromiso del sistema nervioso central. En las últimas décadas, nuevas terapias dirigidas se han posicionado como el estándar de tratamiento y han cambiado la historia natural de esta enfermedad, transformándola en una enfermedad potencialmente curable incluso en etapas avanzadas. Esta revisión busca entregar un resumen de las bases biológicas de esta enfermedad. Por otro lado, dada la aparición de un creciente número de nuevas estrategias de manejo sistémico, nos proponemos revisar sus mecanismos de acción analizando reportes de datos clínicos publicados y la experiencia de nuestro grupo.

Breast cancer (BC) is the leading cause of cancer death for women both worldwide and in Chile. Based on clinical, histological, and molecular features, studies have identified four BC subtypes that correlate with treatment sensitivity. Human Epidermal growth factor Receptor type 2-positive (HER2+) BC represents 15%-25% of newly diagnosed breast neoplasms; HER2+ BC is characterized by its aggressive behavior, early recurrence, and higher risk of brain metastasis. In recent years, HER2-targeted therapies have become the mainstay of treatment and have redefined the natural history of this subtype, reducing relapse rates for early-stage patients and increasing survival in advanced-stage patients. Herein we review novel treatment strategies and their mechanisms of action, along with clinical and real-world data. We also provide a summary of currently available treatments for this subtype and our local experience regarding the management of this disease.

Risk modeling based on HER-2 related genes for bladder cancer survival prognosis assessment / 北京大学学报(医学版)

OBJECTIVE@#To investigate the correlation between the human epidermal growth factor receptor-2-related genes (HRGs) and survival prognosis of bladder cancer and to construct a predictive model for survival prognosis of bladder cancer patients based on HRGs.@*METHODS@#HRGs in bladder cancer were found by downloading bladder tumor tissue mRNA sequencing data and clinical data from the cancer genome atlas (TCGA), downloading HER-2 related genes from the molecular signatures database (MsigDB), and crossing the two databases. Further identifying HRGs associated with bladder cancer survival (P < 0.05) by using single and multi-factor Cox regression analysis and constructing HRGs risk score model (HRSM), the bladder cancer patients were categorized into high-risk and low-risk groups accor-ding to the median risk score. Survival analysis of the patients in high- and low-risk groups was conducted using R language and correlation of HRGs with clinical characteristics. A multi-factor Cox regression analysis was used to verify the independent factors affecting the prognosis of the patients with bladder cancer. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of HRSM was calculated, and a nomogram was constructed for survival prediction of the bladder cancer patients. Analysis of HRSM and patient immune cell infiltration correlation was made using the TIMER database.@*RESULTS@#A total of 13 HRGs associated with patient survival were identified in this study. Five genes (BTC, CDC37, EGF, PTPRR and EREG) were selected for HRSM by multi-factor Cox regression analysis. The 5-year survival rate of the bladder cancer patients in the high-risk group was significantly lower than that of the patients in the low-risk group. High expression of PTPRR was found to be significantly and negatively correlated with tumor grade and stage by clinical correlation analysis, while EREG was found to be the opposite; Increased expression of EGF was associated with high grade, however, the high expression ofCDC37showed the opposite result. And no significant correlation was found between BTC expression and clinical features. Correlation analysis of HRSM with immune cells revealed a positive correlation between risk score and infiltration of dendritic cells, CD8+T cells, CD4+T cells, neutrophils and macrophages.@*CONCLUSION@#HRGs have an important role in the prognosis of bladder cancer patients and may serve as new predictive biomarkers and potential targets for treatment.

Correlation of clinicopathologic features of Filipino primary breast cancer patients with HER2 Subgroups classified according to the ASCO/CAP 2018 breast cancer HER2 testing guidelines

Background@#Guidelines for testing human epidermal growth factor receptor 2 (HER2) in breast cancer using fluorescence in situ hybridization (FISH) were released in 2018. These guidelines were jointly developed by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) to achieve a clearer designation of breast cancer HER2 status. Clinical correlation with other factors was also considered appropriate, especially for those cases classified under ISH groups 2, 3, and 4.@*Objective@#In this study, we examined clinicopathologic features among Filipino breast cancer patients whose HER2 status was reclassified based on the 2018 ASCO/CAP guidelines.@*Methodology@#One hundred and thirty-two (132) breast cancer cases with immunohistochemistry (IHC) equivocal results in the Medical City were enrolled from January 2017 up to December 2020. HER2 FISH results classified under groups 2, 3, and 4 were then re-evaluated for HER2-IHC status in accordance with the 2018 ASCO/CAP guidelines. The relationship between clinicopathologic features and HER2 status was analyzed using the Fisher exact test.@*Results@#Significant differences were found in histologic type, nuclear pleomorphism, mitotic rate, progesterone receptor (PR) status, and regional lymph node involvement among the reclassified ISH groups. In the conv+ group, the tumor cells did not involve the regional lymph nodes as compared to group 5, where the tumor cells were involved. The conv- group had a higher grade for nuclear pleomorphism, mitotic count, and overall Nottingham Histologic Grade than group 5. There was a significant association between progesterone receptors among the conv- group and group 1.@*Conclusion@#Filipino breast cancer cases whose HER2 status was reclassified to negative following the 2018 ASCO/CAP guidelines had statistically different clinicopathologic features from those classified as group 5.

Advances in targeted therapy for HER2-positive breast cancer / 中国临床药理学与治疗学

Since the beginning of the 21st century, with the continuous development of anti-HER2-targeted drugs, more treatment options have been provided for patients with HER2-positive breast cancer and the survival prognosis has been significantly improved. At present, anti-HER2 targeted drugs mainly include monoclonal antibody drugs such as trastuzumab and pertuzumab, small molecule tyrosine kinase inhibitors such as lapatinib and neratinib, and antibody-drug conjugates such as TDM1 and T-DXd, which play an extremely important role in different disease processes. The treatment of HER2-positive breast cancer is based on targeted therapy with trastuzumab. Early-stage patients with high risk factors can be treated with intensive targeted therapy to further improve the prognosis, while advanced patients need a reasonable arrangement of targeted therapy to overcome drug resistance and prolong survival. This article will review the current status, the latest research progress and the future prospects of anti-HER2 targeted therapy in different stages of the disease.

Clinical application and research progress of antibody drugs conjugation in breast cancer / 中国临床药理学与治疗学

Antibody drug conjugations (ADCs) are a new class of drugs with both targeted specificity and high activity of chemotherapy drugs, which has gradually become a novel generation of therapeutic models with great clinical application prospects. In recent years, ADCs composed of monoclonal antibodies against different tumor cell surface antigens and small molecule potent cytotoxic drugs have shown superior therapeutic effects on recurrent / metastatic breast cancer. This article reviews the clinical application and research progress of ADCs with different molecular targets in the field of breast cancer.

Research progress of biomarkers related to the efficacy of HER2 positive breast cancer / 中国临床药理学与治疗学

Breast cancer is the most commonly diagnosed cancer and the main cause of cancer deaths among women worldwide. HER2 positive breast cancer accounts for 15% of all breast cancer. This subtype of breast cancer is highly invasive and has a very poor prognosis. With the development of anti - HER2 targeted therapy, the prognosis of these patients has been improved. However, some patients have poor response to the anti-HER2 therapy. Therefore, it is necessary to select biomarkers that can predict the therapeutic effect for improving the efficacy of these patients. This article describes the research progress of HER2 positive biomarkers for breast cancer, focusing on biomarkers related to the efficacy of targeted therapy, in order to provide some reference for future clinical optimization of 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.

Research progress of targeted therapy for human epidermal growth factor receptor 2 positive gastric cancer / 中国肿瘤生物治疗杂志

@#[摘 要] 以靶向治疗为代表的新兴治疗方法是传统一线放化疗耐药的有效补充，人表皮生长因子受体2（HER2）是胃癌靶向治疗中十分重要的靶点之一，曲妥珠单抗联合化疗已被用于晚期胃癌的一线治疗方案，帕妥珠单抗和马格妥昔单抗治疗胃癌的安全性和有效性已得到了验证。然而，单克隆抗体因其分子量较大、不能穿透血脑屏障，且耐药而导致治疗效果下降，因此需探索其他靶向HER2的疗法在胃癌中的疗效。小分子药物酪氨酸激酶抑制剂（TKI）如拉帕替尼、吡咯替尼等具有分子量小、可穿透血脑屏障和口服生物利用度高等优点，未来经过大型临床试验验证后有望成为胃癌围手术期治疗、新辅助治疗的选择药物。抗体-药物偶联物（ADC）如T-DM1、T-DXd等尽管其发挥肿瘤杀伤作用的机制不同，但能够克服单克隆抗体的耐药，是曲妥珠单抗等单抗治疗失败患者治疗药物的补充。因此，对胃癌患者进行更加细致的分层后，靶向HER2的各类胃癌治疗药物有望发挥更加显著的作用。

Research Progress of HER2 Gene Mutation in Treatment of Breast Cancer / 肿瘤防治研究

HER2 is a tyrosine kinase receptor. It is the main drug target and clinical biomarker for the treatment of breast cancer. About 2% of breast cancer cases has HER2 mutations. Regardless of the expression level or amplification status of HER2, breast cancer with HER2 mutations may respond to targeted HER2 therapy. This article reviews the research progress of HER2 gene mutation in the treatment of breast cancer.

Research Progress of HER2 Positive Colorectal Cancer / 肿瘤防治研究

Epidermal growth factor receptor 2 (HER2) is an oncogene involved in tumour genesis and progression. It is expressed in 7% of patients with colorectal cancer (CRC) and is associated with drug resistance of epidermal growth factor receptor monoclonal antibodies. With the emergence of the therapeutic dilemma of CRC and the survival benefits of targeting HER2 for patients with breast cancer and gastric cancer, the significance of HER2 in CRC and the prognostic value of anti-HER2 therapy have been widely concerned, clinical researches on HER2-positive CRC have been continuously carried out. Currently, the diagnostic criteria for HER2 positive CRC have gradually been unified. HER2-targeting therapies such as monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug coupling and HER2-related immunotherapy alone or in combination have shown good efficacy and brought significant survival benefits for HER2 positive CRC. This paper reviews the research progress of HER2 in CRC.

Reform and Prospect of Systemic Therapy on HER2-positive Early-stage Breast Cancer / 肿瘤防治研究

In the past two decades, the survival of HER2-positive early-stage breast cancer patients has significantly improved with the development of HER2-targeted therapies. The focus has been placed on maximizing the clinical benefit of HER2-positive early-stage breast cancer by optimizing the treatment frameworks and therapeutic strategies in this field. In this paper, several important clinical studies of HER2-positive early-stage breast cancer in the neoadjuvant or adjuvant settings will be summarized and analyzed to provide clues for the development of personalized treatment strategies in the future.

Real-world Efficacy and Safety Comparison of Neoadjuvant Treatment of HER2-positive Breast Cancer with TCbHP Versus AC-THP / 肿瘤防治研究

Objective To compare the efficacy, safety, and survivability of TCbHP versus AC-THP in the neoadjuvant therapy of HER2-positive breast cancer in real-world. Methods Clinical data of patients with HER2 positive breast cancer, who have received TCbHP or AC-THP as neoadjuvant therapy and completed surgery in 11 third-class hospitals in various cities of Hebei Province, were retrospectively collected.The total pathological complete remission (tpCR) rate, the incidence of grade 3 or higher adverse reactions and the completion rate of the given approaches were compared. Results A total of 110 cases were collected, including 78 cases in the TCbHP group and 32 cases in the AC-THP group.The tpCR rate of the TCbHP group was higher than that of the AC-THP group, but the difference was not statistically significant (64.10% vs. 56.25%, P=0.441).No significant difference was found in the breast pathologic complete response (bpCR) and axillary pathologic complete response (apCR) rates between the TCbHP group and the AC-THP group (70.51% vs. 56.25%, P=0.150;78.21% vs. 84.38%, P=0.462).Exploratory analysis revealed that the tpCR rate of the TCbHP group was significantly higher than that of the AC-THP group in patients with HR-positive breast cancer (51.11% vs. 22.22%, P=0.036).As for the patients with HR-negative breast cancer, the tpCR rate of the AC-THP group tended to be higher than that of the TCbHP group (100% vs. 81.82%, P=0.088).The incidence of grade 3 or higher adverse reactions in the TCbHP group was slightly higher than that in the AC-THP group (12.82% vs. 9.38%, P=0.753).No deaths occurred in the whole group.Moreover, no significant difference was observed in the completion rate of the given approaches between the TCbHP group and the AC-THP group (92.31% vs. 90.63%, P=0.718). Conclusion In real-world clinical practice, the neoadjuvant therapy of TCbHP and AC-THP are effective, safe, and well tolerated among patients with HER2-positive breast cancer.The tpCR rate between the two approaches was not significantly different.The AC-THP regimen could also be considered as one of the optimal regimens for HER2-positive breast cancer in neoadjuvant therapy.

c-MET positivity and its relationship with histopathological findings in gastric carcinomas exhibiting HER2 gene expression

Context: Co-expressions of receptor tyrosine kinases such as c-MET and HER2 were reported in many studies. The concomitant expression is associated with more aggressive clinical course. Aims: In this study, it was intended to investigate the correlation of the positivity of c-MET and HER2 with histopathologic findings and their impacts on prognosis. Subjects and Methods: After the decision of the ethics committee, a total of 64 cases, whose HER 2 status was studied by dual silver in situ hybridization/immunohistochemistry method, were included in the study. Immunohistochemical staining for c-MET was performed to all cases and the evaluation was performed similarly to the criteria for HER2 evaluation, but cytoplasmic staining was also considered significant. Statistical Analysis Used: The data were analyzed using SPSS 20 for Windows. Results: c-MET positivity which is considered by the score of 2+ and 3+ was found only in 34.4% of HER2 positive cases while it was 59.3% in HER2 negative cases (P = 0.045). The sole histopathological feature associated with c-MET positivity was distal gastric localization (P = 0.016). Conclusions: Even though higher rates of c-MET positivity in HER2 positive cases were stated in the literature, contrary results were obtained in this study. Comparing the HER2+/c-MET + co-expression group with the other groups, no difference was found about age, sex, macroscopic and microscopic characteristics. The presence of c-MET positivity in cases with HER2 expression suggests that c-MET expression might be associated with the resistance to Trastuzumab.

Effect of HER2 and Fascin expression on muscle-invasive bladder cancers: Classification by basaloid and luminal phenotypes

Purpose: The present study aims to identify basaloid and luminal molecular groups and the p53-like sub-group, which is a sub-group of the luminal group, using a specific immunohistochemical panel and investigate human epithelial growth factor receptor 2 (HER2)/Neu and Fascin expression in these groups to analyze their relationship with clinicopathological features and prognosis in a cohort of cases with muscle-invasive urothelial bladder carcinoma (MIBC). Material and Methods: An immunohistochemical panel that included GATA-3, CK20, CD44, and CK5/6 was used to identify molecular sub-groups based on expression in 44 cases of MIBC. HER2/Neu and Fascin expression in basal, luminal, and p53-like groups and the relationship with clinicopathological features and prognosis were investigated. Results: The distribution of the molecular sub-groups determined by immunohistochemistry was as follows: 23 luminal cases (52.3%), 16 basal cases (36.4%), and 5 (11.4%) p53-like cases. There was a statistically significant difference in tumor size across the groups, with the greatest size in the p53-like group (p = 0.001). A statistically significant difference was observed in HER2/Neu expression between the molecular sub-groups (p = 0.017). Comparison of survival and HER2/Neu scores revealed shorter survival in patients with an HER2/Neu score of 3 + compared to those with scores of 0, 1+, and 2+ (p = 0.109). Fascin immunoreactivity was more common in the p53-like and basal groups compared to the luminal group (p = 0.036). Conclusion: Despite the limited number of cases in the MIBC group, our results support that HER2/Neu expression in the luminal sub-group and Fascin expression in basal and p53-like groups may be used as a negative prognostic marker. Multi-center studies that include large case series are warranted in this field.

Access to HER2?targeted therapy at a tertiary care center in India: An evolution

Background:In a previous retrospective audit from our institution we reported that patients had limited access to HER2-targeted therapy due to financial constraints. Subsequently, the advent of biosimilar versions of trastuzumab and philanthropic support has potentially changed this situation. Herein, we reanalyzed and reported access to HER2-targeted therapy in a more recent cohort of patients. Methods: Medical records of new breast cancer patients registered in one calendar year were retrospectively reviewed, supplemented by online pharmacy data to extract information on receptor status, use of HER2-targeted therapy, and other relevant variables. Since not all HER2 immunohistochemistry (IHC) 2+ tumors underwent fluorescent in-situ hybridization (FISH) testing, we estimated the probable HER2 amplified from this group based on a FISH amplified fraction in those HER2 2+ tumors who did undergo FISH. Results: Between January 2016 and December 2016, 4717 new BC patients were registered at our institution, of whom 729 (20.04%) had HER2 IHC 3+ tumors while 641 (17.62%) had HER2 IHC 2+ tumors. The final number of HER2 overexpressing/amplified tumors was estimated to be 928 (729 HER2 IHC 3+, 105 known FISH amplified, and 94 estimated FISH amplified), of whom 831 received treatment at our institution. Overall 474 (57.03%, 95% confidence interval [CI] 53.6–60.4) of these 831 patients received trastuzumab for durations ranging from 12 weeks to 12 months in the (neo)adjuvant setting or other durations in metastatic setting compared to 8.61% (95% CI 6.2–11.6) usage of HER2-targeted therapy in the 2008 cohort. Conclusion: Access to HER2-targeted therapy has substantially increased among patients treated at a public hospital in the past decade, likely due to the advent of biosimilars, the use of shorter duration adjuvant regimens, and philanthropic support. However, further efforts are required to achieve universal access to this potentially life-saving treatment.