-
ESMO Open Jun 2023Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer is a distinct subtype with different prognosis and response... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer is a distinct subtype with different prognosis and response to treatment. HER2-targeted therapy is currently recommended for patients with HR+/HER2+ advanced breast cancer. However, there is debate over which drugs to add on the basis of HER2 blockade yield the optimal efficacy. This systematic review and network meta-analysis was conducted to solve the problem.
METHODS
Eligible randomized controlled trials (RCTs) comparing different interventions in HR+/HER2+ metastatic breast cancer were included. The outcomes of interest included progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs). Pooled hazard ratios or odds ratios with credible intervals (CrIs) were calculated to estimate the predefined outcomes. The optimal therapeutics were identified by comparing the surface under the cumulative ranking curves (SUCRA).
RESULTS
Totally, 23 literatures of 20 RCTs were included. Regarding PFS, significant differences were detected between single or dual HER2 blockade plus endocrine therapy (ET) versus ET alone and dual HER2 blockade plus ET versus physician's choice. Trastuzumab, pertuzumab plus chemotherapy significantly improved PFS than trastuzumab plus chemotherapy (hazard ratio 0.69, 95% CrI 0.50-0.92). The SUCRA values suggested the relatively better efficacy of dual HER2-targeted therapy plus ET (86%-91%) than chemotherapy (62%-81%) in prolonging PFS and OS. The HER2 blockade-containing regimens showed similar safety profiles in eight documented TRAEs.
CONCLUSIONS
Prominent status of dual-targeted therapy for patients with HR+/HER2+ metastatic breast cancer was revealed. Compared with chemotherapy-containing regimens, the ET-containing ones showed better efficacy and similar safety profiles, which could be recommended in clinical practice.
Topics: Humans; Female; Network Meta-Analysis; Receptor, ErbB-2; Breast Neoplasms; Trastuzumab; Progression-Free Survival
PubMed: 37084609
DOI: 10.1016/j.esmoop.2023.101216 -
BMC Cancer Oct 2023N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear. Therefore, the present study utilized a systematic review and meta-analysis approach to synthesize the association between NDRG1 protein expression and the aggressive characteristics of breast cancer.
METHODS
The protocol for the systematic review and meta-analysis was registered on the PROSPERO website (CRD42023414814). Relevant articles were searched for in PubMed, Scopus, Embase, MEDLINE, and Ovid between March 30, 2023, and May 5, 2023. The included studies were critically evaluated using the Joanna Briggs Institute critical appraisal tools. The results from individual studies were qualitatively synthesized using textual narrative synthesis. Using a random-effects model, the pooled log odds ratio of effect estimate was used to look at the link between NDRG1 protein expression and aggressive features of breast cancer, such as tumor grade, tumor stage, metastasis to the axillary lymph nodes, and hormonal receptor status.
RESULTS
A total of 1423 articles were retrieved from the electronic database search, and six studies that met the eligibility criteria were included for synthesis. There was an association between the expression of NDRG1 protein and the status of the axillary lymph nodes (P = 0.01, log Odds Ratio (OR): 0.59, 95% Confidence Interval (CI): 0.13-1.05, I: 24.24%, 292 breast cancer cases with positive axillary lymph nodes and 229 breast cancer cases with negative axillary lymph nodes, 4 studies). NDRG1 protein expression and human epidermal growth factor receptor 2 (Her2) status were found to have a negative relationship (P = 0.01, log OR: -0.76, 95% CI: -1.32-(-0.20), I: 32.42%, 197 breast cancer cases with Her2 positive and 272 breast cancer cases with Her2 negative, 3 studies). No correlation was found between NDRG1 protein expression and tumor grade (P = 0.10), estrogen receptor (ER) status (P = 0.57), or progesterone receptor (PR) status (P = 0.41).
CONCLUSION
The study concluded that increased NDRG1 protein expression was associated with increased metastasis of the tumor to the axillary lymph node. Additionally, increased NDRG1 protein expression was observed in Her2-negative breast cancer, suggesting its role in both less aggressive and more aggressive behavior depending on breast cancer subtypes. Based on the findings of the meta-analysis, an increase in NDRG1 protein expression was associated with aggressive characteristics of breast cancer.
Topics: Female; Humans; Axilla; Breast Neoplasms; Cell Cycle Proteins; Intracellular Signaling Peptides and Proteins; Lymph Nodes; Receptor, ErbB-2; Receptors, Progesterone
PubMed: 37858101
DOI: 10.1186/s12885-023-11517-7 -
Cancer Medicine Oct 2014There is a small but growing body of literature regarding the predictive utility of a Let-7 microRNA-binding-site polymorphism in the 3'-untranslated region (UTR) of... (Meta-Analysis)
Meta-Analysis Review
There is a small but growing body of literature regarding the predictive utility of a Let-7 microRNA-binding-site polymorphism in the 3'-untranslated region (UTR) of KRAS (KRAS-LCS6) for colorectal cancer outcome, although the results are conflicting. We performed a review and meta-analysis in an attempt to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on KRAS let-7 microRNA-binding site polymorphism (LCS6; rs61764370) and colorectal cancer outcome. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or estimated from each manuscript. Log HRs and log CIs were combined across studies using the inverse-variance weight to calculate fixed- and random-effects summary estimates and corresponding 95% CIs for overall and progression-free survival. We did not observe any significant association between overall or progression-free survival, neither when considering all colorectal cancer patients nor for subgroup analyses (metastatic, anti-EGFR [epidermal growth factor receptor] treatment, or KRAS wild type). There was substantial heterogeneity across studies, overall and among subgroups analyzed. We have found no clear evidence to support an association between the KRAS-LCS6 genotype and overall or progression-free survival among colorectal cancer patients, even after conducting subgroup analyses by stage and anti-EGFR treatment status. This information helps to clarify the confusing body of literature regarding the clinical implications of the KRAS-LCS6 genetic variant on colorectal cancer outcomes, indicating that it should not be used at the present time to personalize therapeutic strategies (PROSPERO registration number: CRD42013005325).
Topics: 3' Untranslated Regions; Binding Sites; Colorectal Neoplasms; Humans; MicroRNAs; Patient Outcome Assessment; Proportional Hazards Models; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins
PubMed: 24890702
DOI: 10.1002/cam4.279 -
International Journal of Molecular... Mar 2024Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex... (Meta-Analysis)
Meta-Analysis Review
Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex with men (MSM) living with HIV underscore the need for effective screening. While high-resolution anoscopy-guided biopsy is the gold standard, limited provider availability poses a challenge. This has spurred interest in identifying biomarkers for improved AC prevention. Antibodies against HPV16 oncoprotein E6, known as markers for cervical and oropharyngeal cancers, are the focus of the current study. The systematic review and meta-analysis included six studies meeting inclusion criteria, assessing HPV16 E6 seroprevalence in individuals with anal HSIL or AC. A two-step meta-analysis estimated pooled odds ratios and 95% confidence intervals (CI) for HPV16 E6 seroprevalence and HSIL or AC. Pooled prevalence, sensitivity, specificity, and diagnostic odds ratios were also calculated. This meta-analysis revealed a 3.6-fold increased risk of HSIL for HPV16 E6 seropositive individuals, escalating to a 26.1-fold risk increase for AC. Pooled specificity and sensitivity indicated a high specificity (0.99; 95%CI: 0.99, 0.99) but lower sensitivity (0.19; 95%CI: 0.10, 0.34) for HPV16 E6 serostatus as an AC biomarker. In conclusion, while HPV16 E6 seroprevalence demonstrates specificity as a potential biomarker for HPV-related AC, its utility as a standalone screening tool may be limited. Instead, it could serve effectively as a confirmation test, particularly in high-risk populations, alongside other diagnostic methods. Further research is imperative to explore HPV16 E6 seroconversion dynamics and alternative screening algorithms.
Topics: Male; Humans; Homosexuality, Male; Human papillomavirus 16; Papillomavirus Infections; Early Detection of Cancer; Seroepidemiologic Studies; Sexual and Gender Minorities; Biomarkers, Tumor; Carcinoma in Situ; Anus Neoplasms; Papillomaviridae
PubMed: 38542409
DOI: 10.3390/ijms25063437 -
Medicina (Kaunas, Lithuania) Mar 2023Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of... (Review)
Review
Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of periodontal regeneration, both in research and clinical practice. Outcomes of histologic studies are particularly valuable when interpreted considering additional evidence available from pre-clinical and clinical studies. One of the best-documented growth factors areproven to have positive effects on a myriad of oral regenerative procedures is recombinant human platelet-derived growth factor-BB (rhPDGF-BB). While a systematic review of clinical studies evaluating rhPDGF in oral regenerative procedures has been recently completed, a review article that focuses on the histologic outcomes is needed. Hence, this communication discusses the histologic effects of rhPDGF-BB on oral and periodontal regenerative procedures, including root coverage and soft tissue augmentation, intrabony defects, furcation defects, peri-implant bone augmentation, and guided bone regeneration. Studies from 1989 to 2022 have been included in this review.
Topics: Humans; Becaplermin; Proto-Oncogene Proteins c-sis; Recombinant Proteins; Intercellular Signaling Peptides and Proteins; Furcation Defects
PubMed: 37109634
DOI: 10.3390/medicina59040676 -
European Journal of Cancer (Oxford,... Nov 2022Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review,... (Review)
Review
BACKGROUND
Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4.
METHODS
A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53.
RESULTS
The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies.
CONCLUSIONS
Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA; DNA-Binding Proteins; Homozygote; Humans; Isocitrate Dehydrogenase; Lymphoma, Follicular; MutS Homolog 2 Protein; Mutation; Phosphatidylinositol 3-Kinases; Sequence Deletion; TOR Serine-Threonine Kinases; Ubiquitin-Protein Ligases
PubMed: 36152406
DOI: 10.1016/j.ejca.2022.08.016 -
Frontiers in Bioscience (Landmark... Jan 2022p38 MAPK (mitogen-activated protein kinases) family proteins (α, β, γ and δ) are key inflammatory kinases and play an important role in relaying and processing...
p38 MAPK (mitogen-activated protein kinases) family proteins (α, β, γ and δ) are key inflammatory kinases and play an important role in relaying and processing intrinsic and extrinsic signals in response to inflammation, stress, and oncogene to regulate cell growth, cell death and cell transformation. Recent studies in genetic mouse models revealed that p38α in epithelial cells mostly suppresses whereas in immune cells it promotes inflammation and inflammation-associated oncogenesis. On the contrary, p38γ and p38δ signaling in immune and epithelial cells is both pro-inflammatory and oncogenic. This review summarizes recent discoveries in this field, discusses possible associated mechanisms, and highlights potentials of systemically targeting isoform-specific p38 MAPKs. Understanding of p38 MAPK isoform-specific and cell/tissue- and perhaps stage-dependent effects and their integrated regulated activity in inflammation and in inflammation-associated oncogenesis is essential for effectively targeting this group of kinases for therapeutic intervention.
Topics: Animals; Carcinogenesis; Inflammation; Mice; Mitogen-Activated Protein Kinases; Protein Isoforms; p38 Mitogen-Activated Protein Kinases
PubMed: 35090336
DOI: 10.31083/j.fbl2701031 -
Journal of Medicine and Life May 2022This study is a systematic review and meta-analysis to assess the overexpression rate of HER2 in patients with salivary gland tumors. We included peer-reviewed... (Meta-Analysis)
Meta-Analysis Review
This study is a systematic review and meta-analysis to assess the overexpression rate of HER2 in patients with salivary gland tumors. We included peer-reviewed publications from 1995 to 2020, indexed in medical databases, using search terms such as "human epidermal growth factor receptor 2 (HER2)" and "salivary gland tumors", and extracted relevant data. The extracted data were analyzed with RevMan 5.3 software. Intra-and intergroup post hoc analyses of outcome variables were performed using t-tests, and the rates of HER2 positivity among studies were evaluated. 80 studies were included in the analysis. The positive rates of HER2 ranged from 3.3% to 84.0% and 1% to 9% in malignant and benign subtypes, respectively. The highest HER2 overexpression rate among malignant tumors was in salivary ductal carcinomas (SDC), with a 45% positive rate (CI 95%: 21.9-70.3%). Mucoepidermoid carcinoma (MEC) had the highest positive rate of 84% (CI 95%: 74.1-90.0%). Among benign salivary gland tumors, the highest rate was found in myoepithelioma, with a positive rate of 9% (CI 95%: 1.7-33.6%). The highest rate of HER2 overexpression is present in malignant subtypes of salivary gland tumors, more specifically in salivary ductal carcinoma, mucoepidermoid carcinomas, salivary duct carcinoma in situ, and carcinoma ex pleomorphic adenoma.
Topics: Biomarkers, Tumor; Carcinoma, Mucoepidermoid; Humans; Receptor, ErbB-2; Salivary Gland Neoplasms; Salivary Glands
PubMed: 35815077
DOI: 10.25122/jml-2021-0394 -
Critical Reviews in Oncology/hematology Apr 2023The benefit of adjuvant trastuzumab treatment in patients with HER2-positive breast tumors ≤ 10 mm without lymph node involvement (T1abN0) is insufficiently... (Meta-Analysis)
Meta-Analysis Review
The benefit of adjuvant trastuzumab treatment in patients with HER2-positive breast tumors ≤ 10 mm without lymph node involvement (T1abN0) is insufficiently investigated. The aim of this systematic review and meta-analysis was to examine if adjuvant trastuzumab improves the prognosis in these patients. Databases were searched to identify interventional and observational studies evaluating the effect of trastuzumab on breast cancer specific survival (BCSS), disease free survival (DFS), distant recurrence free survival (DRFS), overall survival (OS) or recurrence free survival (RFS). Twelve studies examining the effect of trastuzumab and nine control studies without trastuzumab were identified (n = 6927). Median follow-up was 36-123 months. Significantly improved DFS (Hazard Ratio (HR) 0.14, p < 0.0001) and OS (HR 0.17, p = 0.011) were found for patients receiving trastuzumab and chemotherapy compared to no trastuzumab/chemotherapy based on four and two studies. The prognosis was good even for patients without trastuzumab treatment: 5-year DFS 88.3% and 5-year OS 95.9%.
Topics: Humans; Female; Trastuzumab; Receptor, ErbB-2; Breast Neoplasms; Prognosis; Disease-Free Survival; Adjuvants, Immunologic; Chemotherapy, Adjuvant
PubMed: 36854373
DOI: 10.1016/j.critrevonc.2023.103952 -
BMC Cancer Apr 2021Over than one third (28-58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2)...
BACKGROUND
Over than one third (28-58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2) expression. Trastuzumab anti-HER2 monoclonal antibody is still the benchmark treatment of HER2-positive breast tumors. However, FDA has categorized Trastuzumab as a category D drug for pregnant patients with breast cancer. This systemic review aims to synthesize all currently available data of trastuzumab administration during pregnancy and provide an updated view of the effect of trastuzumab on fetal and maternal outcome.
METHODS
Eligible articles were identified by a search of MEDLINE bibliographic database and ClinicalTrials.gov for the period up to 01/09/2020; The algorithm consisted of a predefined combination of the words "breast", "cancer", "trastuzumab" and "pregnancy". This study was performed in accordance with the PRISMA guidelines.
RESULTS
A total of 28 eligible studies were identified (30 patients, 32 fetuses). In more than half of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration during gestation was 15.7 weeks (SD: 10.8; median: 17.5; range: 1-32). Oligohydramnios or anhydramnios was the most common (58.1%) adverse event reported in all cases. There was a statistically significant decrease in oligohydramnios/anhydramnios incidence in patients receiving trastuzumab only during the first trimester (P = 0.026, Fisher's exact test). In 43.3% of cases a completely healthy neonate was born. 41.7% of fetuses exposed to trastuzumab during the second and/or third trimester were born completely healthy versus 75.0% of fetuses exposed exclusively in the first trimester. All mothers were alive at a median follow-up of 47.0 months (ranging between 9 and 100 months). Of note, there were three cases (10%) of cardiotoxicity and decreased ejection fraction during pregnancy.
CONCLUSIONS
Overall, treatment with trastuzumab should be postponed until after delivery, otherwise pregnancy should be closely monitored.
Topics: Adult; Amniotic Fluid; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiotoxicity; Female; Fetus; Humans; Middle Aged; Oligohydramnios; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Trimesters; Receptor, ErbB-2; Time Factors; Trastuzumab; Young Adult
PubMed: 33902516
DOI: 10.1186/s12885-021-08162-3