Frequency Of HER2 Overexpression Research Articles

HER2 Expression Associated with Clinical Characteristics and Prognosis of Urothelial Carcinoma in a Chinese Population.

The frequency of HER2 overexpression in bladder cancer is reported as 9%-61%. HER2 alteration correlates with aggressive disease in bladder cancer. Traditional anti-HER2 targeted therapy has failed to show clinical benefits in patients with advanced urothelial carcinoma . The information on pathologically proven patients with urothelial carcinoma with detected HER2 status was collected from the database of Peking University Cancer Hospital. The HER2 expression, as well as its association with clinical characteristics and prognosis, was analyzed. A total of 284 consecutive patients with urothelial carcinoma were enrolled. HER2 was positive (IHC 2+/3+) in 44% of urothelial carcinoma. HER2 positivity was found more frequent in UCB than in UTUC (51% vs. 38%). Stage, radical surgery, and histological variant were associated with survival (P < .05). For metastatic patients, multivariate analysis shows that 3 indicators, including liver metastasis, the number of involved organs, and anemia, are independent risk factors of prognosis. Receiving immunotherapy or disitamab vedotin (DV) treatment is an independent protecting factor. The survival of patients with low HER2 expression was also significantly improved by the treatment of DV (P < .001). HER2 expression (IHC 1+, 2+, 3+) was associated with a better prognosis in this population. DV has improved the survival of patients with urothelial carcinoma in the real world. With the new-generation anti-HER2 ADC treatment, HER2 expression is no longer a poor prognostic factor.

Long-Term Breast Cancer Outcomes of Pregnancy-Associated Breast Cancer (PABC) in a Prospective Cohort.

Simple SummaryThis study explored the characteristics, treatment, and survival outcomes of patients with pregnancy-associated breast cancer (PABC) in Korea. All patients of this study received standard treatments according to the National Comprehensive Cancer Network guideline. Compared to the non-PABC group, the PABC group had a lower percentage of hormone receptor positivity, increased HER2 overexpression, and higher Ki-67 levels. No maternal complications were observed in patients with PABC. In addition, the 5-year disease-free survival and overall survival rates were significantly poorer in the PABC group than in the non-PABC group. After adjusting for tumor characteristics, PABC was still associated with poor prognosis. This is the first report of the PABC population from a prospective cohort. Exploration to elucidate biologic relevance will follow.Background: Given that peak age of breast cancer (BC) is younger in Asians than in Western populations, relatively higher prevalence of pregnancy-associated breast cancer (PABC) has been reported. This study aimed to analyze the characteristics and clinical outcomes of PABC in Korea. Methods: We defined PABC as BC diagnosed during pregnancy or in the first postpartum year. We compared the clinicopathological characteristics and BC outcomes between patients with PABC and non-PABC patients in the prospective YBC cohort from Samsung Medical Center. Results: In total, 1492 patients were initially enrolled, and 1364 patients were included, of which 93 had PABC (6.8%). The median age of patients with PABC was 34 years. Hormone receptor expression was lower (64.6% vs 74.6%) and frequency of HER2 overexpression was higher (26.9% vs 17.6%) in patients with PABC than in non-PABC patients. The 5-year overall survival (OS) rates were 83.2% and 93.4% in patients with PABC and non-PABC patients, respectively (p < 0.001). The 5-year disease-free survival (DFS) rates were 72.2% and 83.8% in PABC and non-PABC patients. Conclusion: Compared to non-PABC patients, patients with PABC had poorer OS and DFS in this prospective cohort. Exploratory biomarker analysis for PABC is warranted.

Tucatinib: An investigational novel therapeutic agent for the treatment of HER-2 colorectal cancer

Introduction Human epidermal growth factor receptor 2 (HER-2) is an oncogenic driver and target in gastroesophageal and breast cancer; there is also evidence for a role in non-small cell lung cancer (NSCLC). In colorectal cancer (CRC), the incidence of HER-2 overexpression occurs in up to 10% of patients. While its role of HER-2 as a biomarker for prognosis in CRC remains uncertain, it remains of interest as a potential therapeutic target. Tucatinib is an investigational agent which functions as a selective HER-2 inhibitor. Areas covered In this article, the authors discuss the incidence of HER-2 in CRC, and its rationale in the treatment of CRC. An overview of the market is offered, followed by a scientific summary of tucatinib including its clinical development in CRC. Expert opinion Tucatinib is a selective HER-2 inhibitor that has unique properties which distinguishes it from other HER-2 directed therapies. In the clinical setting, it has demonstrated clinical efficacy of HER-2 inhibition across various solid tumors including CRC. Given the evidence of clinical activity observed with tucatinib in breast cancer and frequency of HER-2 overexpression in CRC, the investigation of tucatinib as a monotherapy and in combination with other therapeutic agents remains of interest.

Clinicopathological characteristics of patients with HER2-positive gastric and gastroesophageal junction cancer in a single tertiary hospital.

e16105 Background: Gastric cancer (GC) and gastroesophageal junction cancer (GEJ) are the second most prevalent and lethal digestive malignancies worldwide. According to GLOBOCAN 2020, the incidence in Mexican population is 4.5% and represents 7% of all deaths. In GC and GEJ, the frequency of HER2 overexpression varies widely in the literature. Actually the blocking anti-HER2 is the standard therapy in GC and GEJ with overexpression HER2 according to the ToGa Trial. There are few studies that describe this population in mexican patients. Methods: We conducted a retrospective, observational analysis. Medical records of patients with GC or GEJ cancer from January 2015 to January 2021 were reviewed. A total of 91 patients were retrieved from the pathology database. Clinicalpathologic features collected were sex, age, pTNM stage (AJCC 8th edition), histology type, HER-2 status, metastases sites and treatment. The HER-2 determination was performed in all cases with immunohistochemistry (IHQ). Results: We found 10 patients with GC and GEJ with HER-2 overexpression by IHC, five patients with FISH positive and 2 of them with amplification by next generation sequence (FoundationOne). The median age was 56.9 years (27-68). There were more male patients (n = 8) than female patients (n = 2), with male/female ratio of 4:1. 8 patients had performance status (PS) 0 or 1, and the rest PS 2. The primary site was gastric carcinoma in 3 patients, and in 7 the tumor was located in GEJ. The clinical stage at diagnosis in 7 patients was metastatic, and 3 locally advanced. The most common sites of metastasis were lung (n = 5), liver (n = 4), and pleural, bone and central nervous system (each one with one patient). Intestinal-type GCs were most prevalent with 8 patients, and the rest were diffuse and signet ring cells. All patients received anti-HER2 blockade, 6 in the first line therapy, and 4 patients in the second line or more. Regarding the backbone regimen of the trastuzumab based therapy, fluoropyrimidine/platinum were the mainstay in 9 patients, and 1 with platinum and taxane scheme. Median number of cycles of trastuzumab was 8 (range, 4-24). The tumor responses were as follows: complete response (CR) 10%, partial response (PR) 30%, stable disease 50% and progressive disease 1 patient. The median progression-free survival was 6.6 months (1.3-23.1 months), and a median of overall survival was 21 months (6.4-51.5 months). The most frequently reported adverse events were diarrhoea in 3 patients (all grade 2), and mucositis in 1 patient. Cardiac adverse events were not reported. Conclusions: In our cohort, the prevalence of HER2 overexpression by IHC was 11%. In previous reports, the most important ToGa trial, 22% of the patients with metastatic GC and GEJ were HER2 positive. The PFS and OS in ToGa trial were 13.8 and 17.1 months respectively. By comparison our cohort the PFS and OS in ToGa trial were 6.6 and 21 months.

Frequency and clinical characteristics of HER2 over-expressed breast cancer in Saudi Arabia: a retrospective study

IntroductionThis study aimed to determine the frequency of human epidermal growth factor receptor 2 (HER2) over-expression in newly diagnosed breast cancer (BC) patients in Saudi Arabia and to assess the clinical characteristics and outcomes in patients with HER2-positive disease.MethodsIn the first part of the study, we retrospectively reviewed the pathology records of all patients diagnosed with BC between 2007 and 2013 at 3 hospitals in the largest 3 cities in Saudi Arabia to determine the frequency of HER2 over-expression. In the second part, a representative sample from the patients identified with HER2 over-expressed BC was selected for further investigation. Data collected included demographic and clinical characteristics such as hormone-receptor status, treatment regimens, survival data, response to treatment, and selected adverse events.Results1867 BC records were included in the study. HER2 was overexpressed in 559 patients (29.9%); of those, 348 HER2-positive BC patients were included in subsequent analyses. In the sample of HER2-positive BC patients, median age at diagnosis was 46 years, 0.9% were male, 92.5% were Saudi, 42.4% were Hormone Receptor-negative, and 13.1% had stage IV tumors. Most patients (84.2%) underwent curative intent surgery and 71.8% received radiotherapy. Average tumor size was 3.5 ± 2.5 cm and infiltrating ductal carcinoma was the most common pathology (92.9%). As for pharmacological therapy, the most commonly used regimens were Chemotherapy + Trastuzumab combination (79.1%) in neoadjuvant setting, Hormonotherapy alone (56.2%) in adjuvant setting, and Chemotherapy + Targeted therapy combination (64.8%) as palliative treatment. At the last patient evaluation, 36.9% had complete response, while 33.2% had progressive disease. Median overall survival (OS) and progression-free survival (PFS) were not reached in patients on neoadjuvant/adjuvant pharmacotherapy. As for patients on palliative intent pharmacotherapy, median OS and PFS were 64.7 and 29.3 months respectively.ConclusionThis study provided updated figures regarding HER2 overexpression in BC in Saudi Arabia: HER2 overexpression rate (29.9%) was within the range reported in previous studies. Patients’ demographic and clinical characteristics were also similar to those reported earlier, with a median age at diagnosis of 46 years and one third of patients having locally advanced/metastatic disease at diagnosis.

Comparison of HER-2 Amplification with Clinicopathological and Prognostic Parameters in Metastatic Gastric Carcinomas

Introduction: HER2 overexpression is present in 7 to 34% of gastric carcinomas. Several studies have demonstrated associations between HER2 overexpression and clinicopathological variables, including tumor depth, lymph node metastasis, and intestinal morphology. HER2 overexpression has been linked to shorter survival. Aim: In this study, we aimed to determine the frequency of HER2 overexpression in patients with metastatic gastric carcinoma referred to our clinic, to assess HER2 expression using immunohistochemistry (IHC) or silver in situ hybridization (SISH) and to demonstrate potential associations between HER2 expression and histopathological parameters. Materials and Methods: In this study, we assessed archival samples from 120 patients diagnosed with metastatic gastric carcinoma between 2015 and 2019 and tested for HER2 status. Samples had been obtained by endoscopic biopsy in 84 patients and gastric resection in 36 patients, whereas 36 patients were diagnosed in other health facilities and were referred to our department for consulting. Hematoxylin-eosin stained preparations were reassessed, and diagnoses were confirmed based on World Health Organization (WHO), and Lauren classifications and HER2 results were compared to previous results. HER2 status was assessed by immunohistochemistry (IHC) or silver in situ hybridization (SISH) in available paraffin-embedded tumor sections. Associations between HER2 expression levels and age, sex, tumor location, size and histological type of the tumor, lymphovascular, perineural and perinodal invasion and perinodal invasion, lymph node metastasis, and site of metastasis. Results: 84 (70%) out of 120 patients with metastatic gastric carcinoma were male, and 36 (30%) were female, and the mean age was 60.7 years (age range: 21-90 years). 84 patients had undergone an endoscopic biopsy, and 36 patients had undergone gastric resection, whereas 39 patients were diagnosed in other health facilities and were referred to our department for consulting. In total 31(25.8%) out of 120 subjects tested positive for HER2 overexpression Comparisons of histological patterns, according to Lauren's classification, indicated that intestinal type was predominant in both groups, and none of the diffuse gastric carcinomas was HER2 positive. A statistically significant intergroup difference was found with respect to the prevalence of diffuse gastric carcinoma (p=0.03). Conclusion: In our study, HER-2 gene amplification (25.8%) is compatible with the literature. Her2 positive tumors were mostly located proximally and were not observed in diffuse type. In this respect, they were found statistically significant. Keywords: Her2,SISH,Gastric Carcinoma Original Article: DOI: 10.7176/JHMN/79-07 Publication date: August 31 st 2020

Assessment of two different HER2 scoring systems and clinical relevance for colorectal cancer

Although the positivity of human epidermal growth factor receptor 2 (HER2) is low in colorectal cancer (CRC), anti-HER2 is becoming a new target therapy in metastatic colorectal cancer (mCRC). However, assessment of the HER2 scoring system was still not established in CRC. The purpose of our study was to evaluate HER2 status and its correlation with clinicopathological characteristics and survival according to the HER2 diagnostic criteria for gastroesophageal adenocarcinoma (GEA criteria) and the HERACLES diagnostic criteria (HERACLES criteria) in a large cohort of Chinese CRC patients. The HER2 positivity was 2.9% (43/1490) and 2.6% (39/1490) in CRCs based on the GEA criteria and the HERACLES criteria, and 3.7% (9/243) in mCRC according to both criteria. HER2 status was associated with primary tumor location (P = 0.037), regional lymph node metastasis (P = 0.035), and TNM stage (P = 0.022) in CRCs based on the HERACLES criteria. No such association was found based on the GEA criteria. Furthermore, HER2 positive only presented in patients with RAS gene wild type (P = 0.001). Significant difference was only observed between the HER2-positive and HER2-negative groups in terms of disease-free survival for stage II-III CRCs (P = 0.048) according to the HERACLES criteria, but not based on the GEA criteria. Our findings suggest that the frequency of HER2 overexpression or amplification was low in Chinese CRC patients, and provide a rationale for further evaluation of HER2 in CRC based on the HERACLES criteria and the HER2 diagnostic criteria for gastroesophageal adenocarcinoma.

Abstract 753: Human epidermal growth receptor-2 immunohistochemistry in gastric cancer

Abstract Introduction: Gastric cancer is the second most common GI cancers and third leading cause of cancer-related deaths worldwide. In Ghana, gastric cancer contributes significantly to cancer morbidity and mortality. The recent development on the benefit of targeted therapy in the management of gastric cancer using HER-2 monoclonal antibody in combination with chemotherapy has greatly improved the overall survival of patients. This study therefore aims at determining the frequency of Her-2 over-expression in gastric carcinomas in Kumasi, Ghana and comparing with other prognostic factors. Methodology: Demographic data and histological diagnosis were retrieved from the surgical day book of the Department of Pathology, Komfo Anokye Teaching Hospital, Kumasi. The slides were retrieved and reviewed to confirm diagnosis, grading and classification of gastric cancer. Immunohistochemistry was done with anti-HER-2 antibody to confirm HER-2 over-expression. The data was analysed with SPSS version 17. Results: Of the 99 cases of gastric cancer seen over the 8 year period, there were 57 males and 42 females, adenocarcinoma (91), GIST (5) and Non Hodgskin Lymphoma (3). The age range of the study population was 8-90 years with modal age group in the 6th decade. There were more biopsies (63) than resections (36). Of the adenocarcinomas, 45 were poorly differentiated, 38 moderately differentiated and 8 well differentiated. Diffuse type is most common with 47 cases followed by intestinal 41cases and mixed type 3 cases. Three of the 4 patients under the age of 30 years had lymphoma. HER-2 over-expression was seen in 14 out of the 47 tested and all were intestinal type. Conclusion: HER -2 over-expression was seen a small cohort of our patients with gastric cancer especially those with intestinal type. Citation Format: Babatunde M. Duduyemi, Mary Y. Afihene, Emmanuel A. Asiamah. Human epidermal growth receptor-2 immunohistochemistry in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 753. doi:10.1158/1538-7445.AM2017-753

Characterization of HER2 Gene/Protein and Ki67 Protein Expressions in Colorectal Carcinoma Variants With Relation To Clinicopathological Parameters and Prognosis: An Immunohistochemical and Fluorescence In Situ Hybridization Study

Objective The data on the frequency and pattern of HER2 expression in colorectal carcinoma (CRC) and its clinical signifi¬cance are ambiguous. In addition, little is known about HER2 status in CRC variants and its relation with proliferative activity and clinical outcome. Such knowledge may be of potential value for therapeutic decision making in CRCs. Methods The HER2 gene/protein status was assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in a tissue microarray of 150 CRCs and correlated with the expression of the proliferation marker Ki67, clinicopathological factors, and prognosis. Results CRCs were categorized into conventional adenocarcinoma (CA), 47 cases; adenocarcinoma with mucinous component (AMC), 28 cases; mucinous adenocarcinoma (MA), 56 cases; and signet ring cell carcinoma (SRCC), 19 cases. Compared to other variants, CA was significantly associated with favorable clinicopathological features, higher overall survival (OS) and disease-free survival (DFS), while SRCC and MA were significantly associated with ominous clinicopathological features, lower OS and DFS. Cytoplasmic HER2 overexpression was detected in 14.2% of CRC cases and showed a significant agreement with gene amplification. HER2 overexpression was significantly associated with favorable clinicopathological features notably early stages. High Ki67 expression was detected in 48% of CRC cases. HER2 and Ki67 were significantly different among CRC variants with AMC showing the greatest frequency of HER2 overexpression and Ki67 high expression than the other variants. The interrelation between HER2 and Ki67 expression was statistically insignificant and neither had any significant relation to OS or DFS in any of the CRC variants. Conclusions We conclude that mucinous histology infers an adverse prognosis in CRC. A subset of early stage CRC patients, with HER2 overexpression and possibly a distinct variant, may benefit from HER2 targeted therapy. IHC can be used as a method for screening of HER2 gene amplification in CRCs.

Peritoneal metastatic lesions of gastric cancer exhibit low expression of human epidermal growth factor receptor 2

The prognosis of gastric cancer patients with peritoneal metastasis is very poor. Recent findings suggest that use of trastuzumab, a monoclonal antibody-based agent that targets human epidermal growth factor receptor 2 (HER2), may improve the prognosis of gastric cancer patients with HER2 overexpression and/or gene amplification. However, whether these mechanisms of HER2 upregulation are present in gastric cancer patients with peritoneal metastasis is unclear. The status of HER2 expression in a cohort of samples obtained from 35 gastric cancer patients with peritoneal metastasis was investigated using immunohistochemistry and fluorescence in situ hybridization. In 18 cases, we also investigated the influence of induction chemotherapy on HER2 overexpression. The frequency of HER2 overexpression and gene amplification was 2.9% (1/35) in peritoneal metastatic lesions. There was concurrence in HER2 status in the samples examined prior to and following induction of chemotherapy. Most samples from the gastric cancer patients with peritoneal metastasis did not show HER2 amplification and/or overexpression. Although our study size was small, these results suggest that trastuzumab, which is critically dependent on HER2 expression, might not be an effective agent for these patients. Consequently, other therapeutic approaches for these patients must be developed.

Human epidermal growth factor receptor 2 oncoprotein expression in breast cancer patients from central Anatolia, Turkey

AbstractAim: Human epidermal growth factor receptor 2 (HER2) overexpression is associated with poor prognosis and the frequency of HER2 positivity in breast cancer patients varies among different regions of the world. We studied HER2 expression in Turkish breast cancer patients.Methods: HER 2 expression was evaluated immunohistochemically in 107 breast cancer patients. HER2 expression was reported as negative or positive (3+) according to cellular membrane staining characteristics. The frequency of HER2 overexpression, distribution according to clinical characteristics, effect on survival and effect of chemotherapy on survival in relation to HER2 overexpression was evaluated.Results: The median age of patients was 49 years (range 27–76). HER2 was 3+ in 34 patients (31.8%). There was no significant difference in age, menopausal status, histopathology, lymph node involvement, stage and estrogen and/or progesterone receptor positivity in relation to HER2 expression. Forty‐three patients (40.2%) relapsed and 21 patients (19.6%) died during the follow‐up period. There was no significant difference in the relapse rate, distribution of relapse sites and death rate in relation to HER2 expression. The 3‐ and 5‐year disease free survival rates were 67.1 and 40.5%, and the overall survival rates were 87.5 and 66.1%, respectively. Survival rate and calculated survival time were relatively shorter in HER2 3+ patients than in non‐HER2 3+ patients, but these differences were not statistically significant. HER2 status did not affect survival period according to chemotherapy group.Conclusion: Immunohistochemistry findings of HER2 expression in Turkish breast cancer patients were similar to those found in the published reports. A shorter survival period was observed in HER2 3+ patients, but the difference was not statistically significant.

HER2 protein overexpression in estrogen receptor-positive ductal carcinoma in situ of the breast: frequency and implications for tamoxifen therapy

Recent clinical data have suggested that the efficacy of tamoxifen in reducing the risk of local recurrence following lumpectomy and radiation therapy in patients with ductal carcinoma in situ (DCIS) is limited to patients with estrogen receptor (ER)-positive lesions. However, it is currently not known if HER2 protein overexpression might be associated with reduced tamoxifen benefit in patients with ER-positive DCIS, as has been suggested in patients with ER-positive invasive breast cancer and in preclinical models. Moreover, the frequency of HER2 overexpression in ER-positive ductal carcinoma in situ has not been previously evaluated in detail. To address this issue, we studied ER expression and HER2 overexpression in 148 cases of DCIS using a sensitive double immunostaining technique and assessed the frequency of ER expression and HER2 overexpression in relation to each other and in relation to DCIS grade. Overall, ER expression was seen in 114 cases (77%) and HER2 protein overexpression was seen in 42 cases (28%). Of 114 ER-positive ductal carcinoma in situ, 14 (12%) showed concurrent HER2 protein overexpression, and all 14 of these DCIS lesions were of high nuclear grade. In addition, in all 14 ER-positive DCIS cases that showed HER2 overexpression, double immunostaining demonstrated that ER and HER2 protein were coexpressed by the same neoplastic cells. We conclude that a subset of ER-positive DCIS show concomitant overexpression of HER2 protein. Whether or not HER2 overexpression is associated with a diminished response to tamoxifen in patients with ER-positive DCIS will require investigation in clinical outcome studies.

Expression of HER2 in gastric cancer: Comparison between protein expression and gene amplification using a new commercial kit

4053 Background: Trastuzumab, a monoclonal antibody to HER2 protein, is widely used in patients with HER2-overexpressing breast cancer. Trastuzumab has also shown antitumor activity in human gastric cancer (GC) xenograft models with HER2 overexpression, however, the concordance of protein expression and gene amplification of HER2 in GC cells and the feasibility of using biopsy specimens has not been clarified Aim: The purpose of this study was to evaluate the frequency of HER2 overexpression and the concordance between protein expression and gene amplification in surgical and endoscopic biopsy GC specimens using two commercial immunohistochemical(IHC) kits and fluorescence in situ hybridization (FISH). Materials and Methods: The specimens consisted of formalin-fixed, paraffin-embedded sections of biopsy specimens and surgically resected tumors in 200 cases with invasive GCs who underwent surgery at the National Cancer Center Hospital East. The IHC analysis was performed using the Hercep Test kit (DAKO Cor...