HER2 - Science topic

Purpose: Bone marrow metastasis (BMM) is uncommon in breast cancer (BC), and early diagnosis is challenging. BMM lacks definitive treatment options and poses a great threat to the survival of patients. Herein, we investigated the clinical features, prognosis, and factors affecting the prognosis of BC patients with symptomatic BMM to help improve t...

Background: Disease stage at diagnosis and molecular subtypes are the main determinants of breast cancer treatment strategies and prognosis. We aimed at examining the disparities and factors associated with the stage at diagnosis among the molecular subtypes in breast cancer patients in China. Methods: We identified patients with first primary b...

Background: The changes in prognostic factors and clinicopathological characteristics of residual disease following neoadjuvant therapy (NAT) for breast cancer are important references for postoperative adjuvant therapy. The analyses of the relationship between the clinicopathological characteristics of residual diseases and the prognosis were not...

Purpose Neoadjuvant endocrine therapy (NET) is a treatment option for estrogen receptor-positive (ER+) postmenopausal early breast cancer (EBC). This phase III trial evaluated the prognosis of EBC patients treated with/without chemotherapy (CT) following NET. Methods ER+/HER2−, T1c-2, and clinically node-negative EBC patients were enrolled in 2008...

Background Early identification of response to neoadjuvant chemotherapy (NAC) is instrumental in predicting patients prognosis. However, since a fixed criterion with high accuracy cannot be generalized to molecular subtypes, our study first aimed to redefine grades of clinical response to NAC in invasive breast cancer patients (IBC). And then devel...

Antibody leads must fulfill multiple desirable properties to be clinical candidates. Primarily due to the low throughput in the experimental procedure, the need for such multi-property optimization causes the bottleneck in preclinical antibody discovery and development, because addressing one issue usually causes another. We developed a reinforceme...

In the last decade, cholesterol level has been implicated in several types of cancer, including breast cancer. In the current study, we aimed to investigate the condition of lipid depletion, hypocholesterolemia or hypercholesterolemia reproduced in vitro to analyze the response of different human breast cancer cells. Thus, MCF7 as the luminal A mod...

Background: Anti-HER2 monoclonal antibody is associated with a greater risk of heart failure (HF) in female breast cancer patients. In recent years, the indication of anti-HER2 monoclonal antibodies was further expanded to stomach, colorectal, and salivary gland cancers regardless of sex in Japan. However, there have been no data on sex difference...

Front-line therapy for advanced and metastatic hormone receptor positive (HR+), HER2 negative (HER−) advanced or metastatic breast cancer (mBC) is endocrine therapy with a CDK4/6 inhibitor (CDK4/6i). The introduction of CDK4/6i has dramatically improved progression-free survival and, in some cases, overall survival. The optimal sequencing of post-f...

Introduction: The cytoskeletal protein ezrin is upregulated in many cancer types and is strongly associated with poor patient outcome. While the clinical and prognostic value of ezrin has been previously evaluated in breast cancer, most studies to date have been conducted in smaller cohorts (less than 500 cases) or have focused on specific disease...

Background: ER+HER2+ breast cancer requires most types of systemic therapies perioperatively. However, treatment resistance is often experienced. The current study investigated the predictive and prognostic value of intratumoral heterogeneity and conventional clinicopathological factors in patients with ER+HER2+ breast cancer. Methods: This rese...

The traditional single-treatment strategy for cancer is frequently unsuccessful due to the complexity of cellular signaling. However, suppression of multiple targets is vital to defeat tumor cells. In this research, new compounds for the treatment of cancer were developed successfully as novel hybrid anticancer agents. Based on a molecular hybridiz...

There is little data concerning the implications of PIK3CA mutations outside of the known hotspots described in ER+/HER2− metastatic breast cancer (mBC). Similarly, PIK3R1 mutations could also lead to activation of PI3K pathway, but are poorly described. We determined the incidence and type of all somatic PIK3CA and PIK3R1 mutations by whole exome...

Ovarian cancer is the most lethal gynecological malignancy. Most patients are diagnosed at an advanced stage with widespread peritoneal dissemination and ascites. Bispecific T-cell engagers (BiTEs) have demonstrated impressive antitumor efficacy in hematological malignancies, but the clinical potency is limited by their short half-life, inconvenien...

An accelerated de novo lipogenesis (DNL) flux is a common characteristic of cancer cells required to sustain a high proliferation rate. The DNL enzyme fatty acid synthase (FASN) is overexpressed in many cancers and is pivotal for the increased production of fatty acids. There is increasing evidences of the involvement of FASN in several hallmarks o...

Purpose Tumor-infiltrating lymphocytes (TILs) have been positively correlated with response to systemic therapy for triple-negative and HER2 + subtypes and improved clinical outcomes in early breast cancer (BC). Less is known about TILs in metastatic sites, particularly brain metastases (BM), where unique immune regulation governs stromal compositi...

Circulating tumor cells (CTCs) in the peripheral blood are believed to be the source of metastasis and can be used as a liquid biopsy to monitor cancer progression and therapeutic response. However, it has been challenging to accurately detect CTCs because of their low frequency and the heterogeneity of the population. In this study, we have develo...

Cancer represents a broad spectrum of molecularly and morphologically diverse diseases. Individuals with the same clinical diagnosis can have tumors with drastically different molecular profiles and clinical response to treatment. It remains unclear when these differences arise during disease course and why some tumors are addicted to one oncogenic...

Vulvar Paget’s disease (VPD) is a rare form of cutaneous adenocarcinoma of the vulva, which accounts for about 1–2% of all vulvar neoplasms and mainly affects post-menopausal women. The clinical presentation is usually non-specific and mimics chronic erythematous skin lesions; therefore, the diagnosis is often difficult and delayed. Although VPD is...

Background A few studies have reported the distribution of the microbiota in breast cancer tissues, but few reports have compared the microbiota in different subtypes of breast cancer tissue. Moreover, no study has reported on the relationship between the microbiota and gene expression in breast tumor. Methods Sections of formalin-fixed paraffin-e...

The aim of this study was to assess prevalence of anti-thyroid peroxidase (anti-TPO) antibody and thyroid hormones in Iranian female breast cancer patients, compare them to a control population, and investigate their association with prognostic factors. In this case-control study, breast cancer patients were selected from a surgery clinic in a tert...

Immunotherapy is a developing treatment for advanced breast cancer. Immunotherapy has clinical significance for the treatment of triple-negative breast cancers and human epidermal growth factor receptor-2 positive (HER2+) breast cancers. As a proved effective passive immunotherapy, clinical application of the monoclonal antibodies trastuzumab, pert...

Breast cancer is the most prevalent cancer among women worldwide. The Bloom Richardson grading has been applied to most breast cancers. There are different biologic subtypes of breast cancer according to immunohistochemistry (IHC). Clinically, these subtypes are characterized on the basis of expression of estrogen receptor (ER), progesterone recept...

The treatment provided for breast cancer depends on the expression of hormone receptors, human epidermal growth factor receptor-2 (HER2), and cancer staging. Surgical intervention, along with chemotherapy or radiation therapy, is the mainstay of treatment. Currently, precision medicine has led to personalized treatment using reliable biomarkers for...

Purpose The aim of this study was to estimate the Italian burden of incident breast cancer (BC) by subtypes, according to the distribution of hormonal receptor (HR) status and expression of human epidermal growth factor 2 (HER2). Methods Female breast cancers incidence in the Romagna Unit of the Emilia-Romagna registry (n. 10,711) were grouped int...

Background: Breast cancer (BC) accounts for approximately 24.2% of all malignant tumours in women. Due to advances in chemotherapeutic agents and targeted treatment, survival of BC patients is increasing. Second primary cancers (SPC) are becoming more common, among which lung cancer (LC) has a latency of approximately ten years and may be related t...

Simple Summary: Since the advent of trastuzumab in HER2-positive metastatic breast cancer management , the natural history of this disease continues to improve. The development of molecular biology and better knowledge of the resistance mechanisms of cancer cells have enabled the development of several therapies targeting HER2 and consequently impr...

O trabalho mostrou o tempo de uso de contraceptivo oral correlacionando com os subtipos moleculares do câncer de mama em um Serviço de Oncologia de hospital universitário. Estudo epidemiológico observacional analítico e prospectivo, de delineamento transversal, desenvolvido no Serviço de Oncologia do Hospital Universitário Santa Terezinha (HUST), n...

Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase that plays an oncogenic role in breast, gastric and other solid tumors. However, anti-HER2 therapies are only currently approved for the treatment of breast and gastric/gastric esophageal junction cancers and treatment resistance remains a problem. Here, we engineer an an...

Background: Previous clinical trials indicated the addition of anti-PD-1 antibody remarkably improved the efficacy of trastuzumab and chemotherapy in patients with HER2-positive gastric/gastroesophageal junction (GEJ) cancer. However, no real-world experiences have been reported yet. Methods: We retrospectively analyzed 1212 patients with gastri...

Small molecule Bruton’s tyrosine kinase (BTK) inhibitors have been developed for the treatment of various haemato-oncological diseases, and ibrutinib was approved as the first BTK inhibitor for anticancer therapy in 2013. Previous reports proved the receptor kinase human epidermal growth factor receptor 2 (HER2) to be a valid off-target kinase of i...

Purpose Dysregulation of the PI3K pathway is one of the most common events in breast cancer. Here we investigate the activity of the PI3K inhibitor MEN1611 at both molecular and phenotypic levels by dissecting and comparing its profile and efficacy in HER2 + breast cancer models with other PI3K inhibitors. Methods Models with different genetic bac...

Trastuzumab plus chemotherapy is the standard of care for the first-line treatment of patients with HER2+ advanced esophagogastric (EG) cancer. Nevertheless, patients frequently develop resistance. In preclinical models, we identified the overexpression of Fibroblast Growth Factor Receptor (FGFR) 3 as a mechanism potentially involved in trastuzumab...

Leptomeningeal carcinomatosis is a rare but serious consequence of pre-existing tumors, such as breast, lung, and gastrointestinal carcinomas. Further, leptomeningeal carcinomatosis is more frequently diagnosed with breast cancers, if only because breast cancers are diagnosed far more often than any other carcinomas. In this paper, we present the c...

The chorioallantoic membrane (CAM) assay is an alternative in vivo model that allows for minimally invasive research of cancer biology. Using the CAM assay, we investigated phenotypical and functional characteristics (tumor grade, mitosis rate, tumor budding, hormone receptor (HR) and HER2 status, Ki-67 proliferation index) of two breast cancer cel...

Molecular cancer biomarkers help personalize treatment, predict oncologic outcomes, and identify patients who can benefit from specific targeted therapies. Colorectal cancer (CRC) is the third-most common cancer, with the liver being the most frequent visceral metastatic site. KRAS, NRAS, BRAF V600E Mutations, DNA Mismatch Repair Deficiency/Microsa...

Background: With widespread therapeutic advancement, targeted anticancer therapeutics are taking over traditional treatment protocols. Nevertheless, the resistance to targeted therapeutics has halted the enthusiastic treatment response. An example of targeted therapy is Lapatinib. Lapatinib is a tyrosine kinase inhibitor used in HER2-positive breas...

Background Echocardiograms are recommended every 3 months in patients receiving human epidermal growth factor 2 (HER2)-targeted therapy for surveillance of left ventricular ejection fraction (LVEF). Efforts to tailor treatment for HER2-positive breast cancer have led to greater use of non-anthracycline regimens that are associated with lower cardio...

Breast cancer (BC) among premenopausal women is an aggressive disease associated with poor outcome despite intensive treatment. Higher burden is observed in southeast Asian countries attributed to younger population structure. We compared the reproductive and clinicopathological characteristics, distribution of subtypes and survival between pre and...

Xpert Breast Cancer STRAT4 is a RT-qPCR platform that studies the mRNA expression of ESR1, PGR, MKI67 and ERBB2, providing a positive or negative result for each of these breast cancer biomarkers. Its concordance with immunohistochemistry (IHC) and in situ hybridization (ISH) has been previously demonstrated, but none of the previous works was focu...

Introduction and importance Soft tissue metastases from any primary malignant tumor are considered very rare and can be found in subcutaneous or muscle tissue. We present the fifth case of breast cancer (BC) metastasis in subcutaneous tissue of the back and with an interval of 15 years between its detection and the diagnosis of BC. Case presentati...

This multicenter registry study aims to analyze time-related changes in the treatment patterns and outcome of patients with metastatic breast cancer (MBC) over a ten-year period. Correlations between demographic, prognostic variables and survival outcomes were carried out in database aggregates consisting of cohorts based on disease presentation (r...

Background The success of HER2-positive (HER2+) breast cancer treatment with trastuzumab, an antibody that targets HER2, relies on immune response. We demonstrated that TNFα induces mucin 4 (MUC4) expression, which shields the trastuzumab epitope on the HER2 molecule decreasing its therapeutic effect. Here, we used mouse models and samples from HER...

C/EBP homologous protein (CHOP), also known as DNA damage-inducible transcript 3 (DDIT3), is a member of CCAAT/enhancer-binding protein (C/EBP) family. The expression of CHOP is upregulated during unfolded protein response (UPR), and sustained CHOP activity plays an important role in UPR-induced apoptosis. MicroRNA-616 is localized in an intron of...

Background Breast malignancies are now the most common and deadliest type of neoplasms among women worldwide. Novel therapeutic approaches are needed to combat advanced stages of breast cancer. In this study, we aimed to investigate the expression and co-expression status of three immune checkpoints (PD-1, PD-L1, and LAG-3), as well as tumor-infilt...

Background Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the indivi...

Metaplastic breast cancer (MpBC) is a rare, aggressive type of breast cancer, often classified as triple negative (TN). Scarce information is available about germline testing in MpBC. We retrospectively reviewed MpBC patients counseled at our Institute and found to harbor germline pathogenic variants (PVs), and we revised literature data. We identi...

Cardiovascular (CV) diseases (CVD) are a major cause of long-term morbidity and mortality affecting life expectancy amongst cancer survivors. In recent years, because of the possibility of early diagnosis and the increased efficacy of neo-adjuvant and adjuvant systemic treatments (targeting specific molecular pathways), the high percentage of survi...

Although shown to be effective in improving survival and quality of life in patients with cancer, some treatments are well-known causes of cardiotoxicity, such as anthracyclines, monoclonal antibodies against human epidermal growth factor receptor 2 (HER2) and radiotherapy. To prevent cardiovascular disease (CVD) in patients living with cancer, car...

Background To our current understanding, solid tumors depend on suppressed local immune reactions, often elicited by the interaction between tumor cells and tumor microenvironment (TME) components. Despite an improved understanding of anti-cancer immune responses in the TME, it is still unclear how immuno-suppressive TME are formed and how some can...

Введение. Группа РМЖ с тройным негативным фенотипом (РМЖЭР–/ПР–/HER2–) неоднородна. По ранним представлениям клиницистов анти-HER2-таргетная терапия не может быть использована при РМЖЭР–/ПР–/HER2–. С клинической разработкой новых конъюгатов на основе анти-HER2–антитело-линкер-цитостатик, эксперты все чаще высказываются за необходимость пересмотра к...

Background: The Phase 3 CT-P6 3.2 study demonstrated equivalent efficacy and comparable safety between CT-P6 and reference trastuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer after up to 3 years' follow-up. Objective: To investigate long-term survival with CT-P6 and reference trastuzumab. Me...

Triple-negative breast cancer accounts for 10-15% of all breast tumors (TNBC). Triple-negative breast cancer lacks either estrogen or progesterone receptors (ER or PR), producing either too little or too much HER2. (All three tests result in "negative" results for the cells.) These cancers are more common in women under 40 who are Black or have the...

Background We previously reported Minichromosome maintenance 4 (MCM4) overexpression in gastric cancer. However, the clinicopathological significance of MCM4 in urothelial carcinoma (UC) has not been investigated. To clarify the clinicopathological significance of MCM4 in UC, we investigated MCM4 expression with immunohistochemistry (IHC). Methods...

Background Inflammatory bowel disease (IBD) patients with an ileo-anal pouch anastomosis (IPAA) bear an increased risk of pouch neoplasia, with prior colorectal neoplasia as the strongest predictor. It is unknown if pouch neoplasia develops independently or is derived from prior colorectal neoplasia. Purpose We aimed to assess potential clonality...

Рак желудка – это злокачественное заболевание с низкой общей выживаемостью, характеризующееся, в ряде случаев, агрессивным течением, несмотря на современные достижения хирургии, химиотерапии, молекулярно-генетических технологий. В связи с тем, что результаты лечения по-прежнему крайне неудовлетворительные, поиск новых терапевтических мишеней стал з...

Recently, targeted nanoparticles (NPs) have attracted much attention in cancer treatment due to their high potential as carriers for drug delivery. In this article, we present a novel bioconjugate (DOX–AuNPs–Tmab) consisting of gold nanoparticles (AuNPs, 30 nm) attached to chemotherapeutic agent doxorubicin (DOX) and a monoclonal antibody, trastuzu...

Активирующие мутации в гене PIK3CA при гормонозависимом HER2-негативном (HR+ HER2–) метастатическом раке молочной железы (РМЖ) ассоциированы с повышенной частотой метастазирования в головной мозг (ГМ). Данные об эффективности таргетных препаратов при метастатическом поражении головного мозга, особенно при активных симптомных метастазах, ограничены,...

Objectives: The aim of the study was to assess patients belonging to four main molecular subtypes (Luminal A, Luminal B, HER2 neu positive and Triple negative) and their treatment plans with a view to compare their early surgical complications and the final outcomes specific to the surgical procedure adopted and molecular subtype. Methods: A Cross-...

De novo metastatic breast cancer (dnMBC) accounts for ~6–10% of all breast cancers and for ~30% of MBC with increasing incidence over time. Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) tumours are the most frequent subtype with a similar incidence to that observed amongst recurrent MBC (rMBC). Higher frequ...

The lack of estrogen or progesterone receptors and absence of HER2 amplification/overexpression in triple-negative breast cancer (TNBC) restricts therapeutic options used in clinical management. MicroRNAs (miRNAs) are small, non-coding transcripts which affect important cellular mechanisms by regulating gene expression at the post-transcriptional l...

Ki67, a marker of cellular proliferation, is commonly assessed in surgical pathology laboratories. In breast cancer, Ki67 is an established prognostic factor with higher levels associated with worse long-term survival. However, Ki67 IHC is considered of limited clinical use in breast cancer management largely due to issues related to standardizatio...

The use of Cyclin Dependent Kinase 4/6 inhibitors (CDK4/6i) induce transcription in breast tumors. The control mechanism of such genomic changes and their physiological relevance are not elucidated yet. Now, we identified chromatin activation of tumors treated with CDK4/6i. These chromatin changes induce an increase of HER2 expression and signaling...

Purpose To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) heavily pretreated with anthracycline and taxanes. Methods In this single-arm, phase II study, patients with HER2-negative MBC previously treated with anthracy...