-
Frontiers in Oncology 2024Patients with metastatic HER2-positive breast cancer have multiple therapeutic options. However, most are not studied in the renal replacement therapy (RRT) setting.
INTRODUCTION
Patients with metastatic HER2-positive breast cancer have multiple therapeutic options. However, most are not studied in the renal replacement therapy (RRT) setting.
CASE REPORT
We report the use of Phesgo® (subcutaneous fixed-dose combination of trastuzumab and pertuzumab) combined with exemestane as a first-line treatment of metastatic HER2-positive breast cancer in a hemodialysis patient with multiple comorbidities. Partial response was attained, with disease progression after 8 months without evidence of significant toxicity.
DISCUSSIONS
This case report is, to our knowledge, the first published case documenting the use of Phesgo® in a hemodialysis patient. No new safety signs were seen, and activity was documented, adding support to the use of this drug combination in such a patient population.
PubMed: 38774415
DOI: 10.3389/fonc.2024.1348343 -
Frontiers in Oncology 2024The overamplification of human epidermal growth factor (HER2) in breast cancer (BC) has been the subject of numerous research publications since its discovery in 1987.... (Review)
Review
AIM
The overamplification of human epidermal growth factor (HER2) in breast cancer (BC) has been the subject of numerous research publications since its discovery in 1987. This is the first bibliometric analysis (BA) conducted on HER2-positive (HER2+) BC. The purpose of this BA is to analyze the published research on HER2+ BC from 1987 to 2024, highlighting the most significant scientific literature, as well as the main contributing authors and journals, and evaluating the impact of clinical and lab-based publications on HER2+ BC research.
METHODS
The Web of Science Core Collection (WoSCC) was searched using the terms "Breast cancer" OR "Breast carcinoma" OR "Breast tumor" AND "HER2 positive" OR "HER2+". The search was limited by publication year (1987-2024) and only full English articles were included. WoS returned 7,469 relevant results, and from this dataset, a bibliometric analysis was conducted using the "analyze results" and "journal citation report" functions in WoS and the VOSviewer 1.6.16 software to generate bibliographic coupling and co-citation analysis of authors.
RESULTS
The analysis encompassed a total of 7,469 publications, revealing a notable increase in the annual number of publications, particularly in recent years. The United States, China, Italy, Germany, and Spain were the top five most prolific countries. The top five significant institutions that published HER2+ research were the University of Texas System, Unicancer, UTMD Anderson Cancer Center, Harvard University, and University of California System. , , and were the top three notable journals with the highest number of HER2+ BC publications. Dennis Slamon (Nc = 45,411, H-index = 51) and Jose Baselga (Nc = 32,592, H-index = 55) were the most prolific authors. Evolving research topics include anti-HER2 therapy in the neoadjuvant setting, treatment of metastatic HER2+ BC, and overcoming therapy resistance.
CONCLUSION
This study provides an overview of HER2+ BC research published over the past three decades. It provides insight into the most cited papers and authors, and the core journals, and identifies new trends. These manuscripts have had the highest impact in the field and reflect the continued evolution of HER2 as a therapeutic target in BC.
PubMed: 38769947
DOI: 10.3389/fonc.2024.1355353 -
Journal of Breast Cancer Apr 2024The global incidence of breast cancer is on the rise, a trend also observed in South Korea. However, thanks to the rapid advancements in anticancer therapies, survival... (Review)
Review
The global incidence of breast cancer is on the rise, a trend also observed in South Korea. However, thanks to the rapid advancements in anticancer therapies, survival rates are improving. Consequently, post-treatment health and quality of life for breast cancer survivors are emerging as significant concerns, particularly regarding treatment-related cardiotoxicity. In this review, we delve into the cardiovascular complications associated with breast cancer treatment, explore surveillance protocols for early detection and diagnosis of late complications, and discuss protective strategies against cardiotoxicity in breast cancer patients undergoing anticancer therapy, drawing from multiple guidelines.
PubMed: 38769686
DOI: 10.4048/jbc.2024.0085 -
Frontiers in Pharmacology 2024As a novel drug formulation, antibody drug conjugates (ADCs) are widely used in various types of cancer. However, clinically, there is a lack of attention to the CVD...
OBJECTIVE
As a novel drug formulation, antibody drug conjugates (ADCs) are widely used in various types of cancer. However, clinically, there is a lack of attention to the CVD produced by them, as well as a lack of research on the real-world situation. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to ensure its clinical safety application, we analyzed post-marketing data on antitumor ADCs to identify risk factors and drugs associated with the risk of cardiovascular events.
RESEARCH DESIGN AND METHODS
We used OpenVigil 2.1 to conduct a database query for adverse events (AEs) reported to the FAERS database between the time the drug was launched and the second quarter of 2023. Cardiovascular adverse events (AEs) were grouped into fourteen narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs), and the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and cardiovascular disease (CVD) risk were calculated.
RESULTS
In the FAERS database, 1863 AEs associated with CVD we studied were identified in patients receiving ADC therapy. Most reports came from people aged ≥65, but a significant number of cases were found to be unknown. The number of patients with antibody-drug conjugates (ADCs)-related CVD cases aged <18 years, 18-64 years, and≥ 65 years was 52 (2.79%), 586 (31.45%), and 613 (32.90%), respectively. The proportion of female patients (834, 44.77%) was higher than that of male patients (752, 40.37%). Death (770 reports), disability (9 reports), Hospitalization initial or prolonged (407 reports), and life-threatening reactions (187 reports). Of the 770 deaths reported, 103 (31.7%) were associated with brentuximab vedotin, 10 (24.4%) with sacituzumab govitecan, 22 (19.3%) with enfortumab vedotin, and 35 (34.7%) with trastuzumab emtansine.49 (41.2%) cases were associated with polatuzumab vedotin, 62 (29%) with trastuzumab deruxtecan, 423 (54.3%) with gemtuzumab ozogamicin, and 66 (38.8%) with inotuzumab ozogamicin. In a disproportionate number of SMQS, cardiac failure ( = 277) and embolic and thrombotic events, venous ( = 446) were the most frequently reported CVD-related AEs in ADCs.
CONCLUSION
By mining the FAERS database, we provided relevant information on the association between ADC use and cardiovascular-associated AEs. ADCs were associated with increased cardiovascular toxicity, deserving distinct monitoring and appropriate management. Further research is needed to confirm these findings and assess causality.
PubMed: 38766629
DOI: 10.3389/fphar.2024.1378010 -
World Journal of Oncology Jun 2024The first-line treatment for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) involves a combination of trastuzumab, pertuzumab,...
BACKGROUND
The first-line treatment for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) involves a combination of trastuzumab, pertuzumab, and a taxane (TPH). This study assessed the efficacy of trastuzumab and pertuzumab (PH) in routine practice, following the treatment protocols of Uruguay's National Resources Fund (FNR), akin to clinical trials.
METHODS
Patients with advanced MBC treated with PH between 2008 and 2022 per FNR protocols were evaluated. The Kaplan-Meyer method and log-rank test were utilized for analyzing overall survival (OS). Demographic and clinical variables, including age, menopausal status, and hormone receptors (HR), were analyzed.
RESULTS
The study included 318 PH-treated patients. The median age was 56 years, with 63.2% being postmenopausal and 60.4% HR and HER-2 positive. With a median follow-up of 17.2 months, the median OS was 29 months. OS varied based on HR status and the presence of metastases at different sites, significantly lower in patients with brain, cutaneous/subcutaneous, and pulmonary metastases. Additionally, OS was higher in patients treated at private institutions compared to public ones.
CONCLUSIONS
This study demonstrates the disparity in oncological treatment efficacy between clinical trials and clinical reality in Uruguay, emphasizing the importance of authentic environment research for more representative and effective medicine in Latin America.
PubMed: 38751695
DOI: 10.14740/wjon1829 -
Translational Breast Cancer Research :... 2024Recently, human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) has emerged as a novel subset within the category of HER2-negative BC, prompting a... (Review)
Review
Recently, human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) has emerged as a novel subset within the category of HER2-negative BC, prompting a reassessment of the immunohistochemical negative scores of 0, 1+, and the 2+/in situ hybridization (ISH) negative phenotype. Recent clinical trials have provided compelling evidence of the substantial clinical advantages offered by novel antibody-drug conjugates (ADCs) that target HER2 in the treatment of these specific tumor cohorts. Notably, trastuzumab deruxtecan (T-Dxd), an ADC that specifically targets HER2, has recently received approval from the US Food and Drug Administration as the inaugural targeted therapeutic option for HER2-low BC. However, the classification of HER2-low BC as a distinct subtype, the methods for detecting HER2-low BC, and the optimal treatment approach for HER2-low BC remain subjects of ongoing debate and lack consensus. This comprehensive review aims to address these pertinent concerns, offering insights into the nuanced tumor biology underlying HER2-low BC and critically analyzing the current treatment pathways available. By synthesizing available evidence, the objective is to contribute to an enhanced understanding of HER2-low BC, providing a foundation for more informed clinical decisions and further advancements in tailored therapeutic approaches. As the medical community navigates these uncertainties, this review seeks to consolidate existing knowledge, fostering a collective effort toward establishing consensus in the diagnosis and treatment of HER2-low BC.
PubMed: 38751682
DOI: 10.21037/tbcr-23-48 -
Translational Breast Cancer Research :... 2023We report a case of metastatic human epidermal growth factor receptor-2 (HER2) positive breast cancer who achieved encouraging clinical benefits across multiple...
BACKGROUND
We report a case of metastatic human epidermal growth factor receptor-2 (HER2) positive breast cancer who achieved encouraging clinical benefits across multiple pyrotinib-based anti-HER2 therapies.
CASE DESCRIPTION
A 33-year-old woman was diagnosed with hormone receptor (HR) positive, HER2-positive breast cancer in June 2018, and did not receive adjuvant radiotherapy, chemotherapy, or anti-HER2 targeted therapy post-breast conserving surgery. By May 2020, she developed recurrence of the left breast mass with metastases in liver, bone and lymph nodes. She then received pyrotinib plus trastuzumab and nab-paclitaxel as first-line therapy. Both the left breast mass and liver metastases showed noticeable improvement, with the disease evaluated as partial response (PR). Despite this promising result, the patient developed brain metastases after first-line treatment. A combination regimen of pyrotinib retention plus inetetamab and vinorelbine were administered as second-line anti-HER2 therapy, and the brain metastases visibly shrunk, leading to PR, with the extracranial lesions remaining stable. Ultimately, due to brain lesions progression, the treatment was transitioned to trastuzumab deruxtecan. We applied next generation sequencing (NGS) to illustrate the efficacy of anti-HER2 therapy and minimal residual disease (MRD) to detect the disease status.
CONCLUSIONS
Pyrotinib is a promising antineoplastic agent for HER2-positive advanced breast cancer patients. Under the guidance of precision medicine, it is encouraged to utilize novel diagnostic and therapeutic methods to manage advanced breast cancer patients.
PubMed: 38751473
DOI: 10.21037/tbcr-23-26 -
Chinese Journal of Cancer Research =... Apr 2024Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2 (HER2)-positive (+) breast cancer patients and remains a clinical...
OBJECTIVE
Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2 (HER2)-positive (+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.
METHODS
HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells and a xenograft mouse model with primary resistance to trastuzumab.
RESULTS
Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.
CONCLUSIONS
Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.
PubMed: 38751436
DOI: 10.21147/j.issn.1000-9604.2024.02.03 -
Discover Oncology May 2024Neutrophil elastase (NE) is a proteolytic enzyme released extracellular during the formation of neutrophil extracellular traps (NETs) through degranulation. In addition... (Review)
Review
Neutrophil elastase (NE) is a proteolytic enzyme released extracellular during the formation of neutrophil extracellular traps (NETs) through degranulation. In addition to participating in the body's inflammatory response, NE also plays an important role in cancer. It can promote tumor proliferation, migration, and invasion, induce epithelial-mesenchymal transition (EMT), and change the tumor microenvironment (TME) to promote tumor progression. Concurrently, NE promotes systemic treatment resistance by inducing EMT. However, it can also selectively kill cancer cells and attenuate tumor development. Sivelestat is a specific NE inhibitor that can be used in the perioperative period of esophageal cancer patients to reduce the incidence of postoperative complications after esophagectomy. In addition, the combination of sivelestat and trastuzumab can enhance the efficacy of human epidermal growth factor receptor 2(HER 2) positive breast cancer patients. Meanwhile, targeting the human antibody domains and fragments of NE is also a new way to treat cancer and inflammation-related diseases. This review provides valuable insights into the role of NE in cancer treatment. Additionally, we discuss the challenges associated with the clinical application of sivelestat. By shedding light on the promising potential of NE, this review contributes to the advancement of cancer treatment strategies.
PubMed: 38750338
DOI: 10.1007/s12672-024-01010-3 -
Research Square Apr 2024In 2008, bevacizumab received accelerated Food and Drug Administration (FDA) approval for use in human epidermal growth factor receptor 2 (HER2)-negative metastatic...
A randomized phase III double-blind placebo-controlled trial of first line chemotherapy and trastuzumab with or without bevacizumab for patients with HER2/neu-positive metastatic breast cancer: a trial of the ECOG-ACRIN Cancer Research Group (E1105).
BACKGROUND
In 2008, bevacizumab received accelerated Food and Drug Administration (FDA) approval for use in human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Based on the preclinical and preliminary clinical activity of the trastuzumab and bevacizumab combination, ECOG-ACRIN E1105 trial was developed to determine if the addition of bevacizumab to a chemotherapy and trastuzumab combination for first-line therapy would improve progression-free survival (PFS) in patients with HER2-positive MBC.
FINDINGS
96 patients were randomized to receive standard first-line chemotherapy and trastuzumab with or without bevacizumab between November 2007 and October 2009, and 93 began protocol therapy. Induction therapy was given for 24 weeks, followed by maintenance trastuzumab with or without bevacizumab. 60% (56/93) began carboplatin and 74% (69/93) completed 6 cycles of induction therapy. Primary endpoint was PFS. Median PFS was 11.1 and 13.8 months for placebo and bevacizumab arms, respectively (hazard ratio [HR] 95%, Confidence Interval [Cl] for bevacizumab vs. placebo: 0.73 [0.43-1.23], p = 0.24), and at a median follow-up of 70.7 months, median survival was 49.1 and 63 months (HR [95% Cl] for OS: 1.09 [0.61-1.97], p = 0.75). The most common toxicities across both arms were neutropenia and hypertension, with left ventricular systolic dysfunction, fatigue, and sensory neuropathy reported more frequently with bevacizumab.
CONCLUSIONS
In this trial, the addition of bevacizumab did not improve outcomes in patients with metastatic HER2-positive breast cancer. Although the trial was underpowered due to smaller than anticipated sample size, these findings corroborated other clinical trials during this time.
PubMed: 38746356
DOI: 10.21203/rs.3.rs-4295044/v1