Search Results (341)

Background: The human body’s exposure to high levels of endogenous estrogens and their metabolites, such as estradiol, estriol, 2-hydroxyestradiol, and 4-hydroxyestradiol, is implicated in the development and complications of breast cancers (BCs). Besides endogenous estrogen production, the human body is also exposed to environmental sources of estrogen and estrogen-like compounds, which include pharmaceutical estrogens, xenoestrogens, and phytoestrogens. Females consume pharmaceutical estrogens as a constituent of postmenopausal hormone replacement therapy (HRT) and oral contraceptive pills, either alone or in combination with progestins. Additionally, humans, including females, are exposed to estrogen-resembling non-native compounds called xenoestrogens, prevailing in pesticides, plastics, and personal care items via inhalation, dermal contact, and oral consumption. Several phytoestrogens, such as isoflavones and lignans, are consumed by humans as food ingredients. Methods and Results: Emerging cellular and molecular experimental evidence indicates that when binding to estrogen receptors (ERs), various pharmaceutical estrogens, including equine/synthetic forms, progestin combinations, and xenoestrogens, promote BC development and complications by triggering survival, proliferation, angiogenesis, and invasion of these cells. Conversely, other experimental observations reveal the protective and beneficial effects of phytoestrogens like genistein from soy products on BC development and complications. Conclusions: This comprehensive review article describes the implications of exposure to exogenous estrogens, such as pharmaceutical estrogens, xenoestrogens, and phytoestrogens, as risk factors in the prevention or development of BC and its complications. Full article

Objectives: The aim of this study was to determine the differential temperature produced on ceramic implants using laser irradiation on a pulsed setting of intrabony defects in vitro. Methods: A ceramic (Zr) dental implant (Zeramex, 4.8 × 12 mm) was placed into a bovine bone block. A three-wall intrabony defect (6 × 4 × 3 mm) was created to mimic an osseous peri-implant defect. Thermocouples were placed on the apical and coronal areas to measure temperature changes (∆T) during 60 s of laser irradiation. The bovine block was heated to 37 °C, and the defect walls were irradiated with the CO₂ and Er,Cr:YSGG laser. The settings used were pulsed mode for both lasers, with 30 Hz and 1.5 W for the Er,Cr:YSGG laser and 70 Hz and 2 W for the CO₂ laser. The same laser settings were repeated at room temperature (RT, 23 °C). Twenty trials were performed for each experimental group at room and body temperature for assessment of ∆T. Paired t-test were used to compare the measurements between 37 °C and 23 °C for the Er,Cr:YSGG, and CO₂ laser, respectively. Results: The CO₂ laser resulted in the highest ∆T (°C) at the coronal (15.22 ± 0.28/8.82 ± 0.21) and apical (5.84 ± 0.14/2.30 ± 0.28) level when this laser was used in both room temperature and body temperature, respectively. The highest ∆T (°C) for the Er,Cr:YSGG laser at body temperature at the coronal thermocouple was 7.64 ± 0.55, while for the CO₂ laser, at body temperature was 8.82 ± 0.21. Conclusion: Within the limitations of our study, the use of CO₂ laser and Er,Cr:YSGG laser on peri-implant defects generally appears to be safe in treating peri-implant defects around zirconia implants in vitro. Full article

Estrogens regulate many physiological processes in the human body, including the cardiovascular system. Importantly, Estradiol (E2) exerts its vascular protective actions, in part, by promoting endothelial repair via induction of endothelial cell (EC) proliferation, migration and angiogenesis. Recent evidence that microRNAs (miRNAs) play an important role in vascular health and disease as well as in regulating Estrogen actions in many cell types. We hypothesize that E2 may mediate its vascular protective actions via the regulation of miRNAs. Following initial screening, we found that E2 downregulates the levels of miR-193a-3p in ECs. Moreover, miR-193a-3p downregulation by miR-193a-3p-antimir mimicked the effects as E2 on EC growth, migration, and capillary formation. Restoring miR-193a-3p levels with mimics after E2 treatment abrogated the vasculogenic actions of E2, suggesting a key role of miR-193a-3p in E2-mediated EC-growth-promoting effects. We further investigated the cellular mechanisms involved and found that miR-193a-3p inhibits angiogenesis by blocking phosphoinositide-3-kinase (PI3K)/Akt-vascular endothelial growth factor (VEGF) and Activin receptor-like kinase 1 (ALK1)/SMAD1/5/8 signaling in ECs, both pathways that are important in E2-mediated vascular protection. Additionally, using reverse transcription polymerase chain reaction (RT-PCR), we demonstrate that E2 downregulates miR-193a-3p in ECs via Estrogen Receptor (ER)α, but not ERβ or G protein-coupled estrogen receptor (GPER). Moreover, these actions occur post-transcriptionally, as the expression of pri-miR-193a-3p was not affected. The anti-angiogenic actions of miR-193a-3p were also observed in in vivo Matrigel implant-based capillary formation studies in ovariectomized mice where E2 induced capillary formation, and these effects were abrogated in the presence of miR-193a-3p, but not in the control mimic. Assessment of miR-193a-3p levels in plasma collected from in vitro fertilization (IVF) subjects with low and high E2 levels showed significantly lower miR-193a-3p levels in responders during the high E2 period. Hence, our findings provide the first evidence that miR-193a-3p mimic inhibits angiogenesis whereas its antimir is angiogenic. Importantly, E2 mediates its regenerative actions on ECs/capillary formation by downregulating endogenous miR-193a-3p expression. Both miR-193a-3p mimic or antimir may represent important therapeutic molecules to prevent or to induce endothelial function in treating pathophysiologies associated with capillary growth. Full article

Background/Objectives: Apolipoprotein E receptor-2 (apoER2) exists in various alternatively spliced forms, including variants that express apoER2 with or without exon 19 in the cytoplasmic domain. This study compared vascular response to endothelial denudation, as well as diet-induced atherosclerotic and metabolic diseases, between genetically modified mice that exclusively expressed the apoER2 splice variant with or without exon 19 to determine the impact of apoER2 exon 19 motif in cardiometabolic disease modulation. Methods: Vascular response to injury was assessed by measuring neointima area of the carotid arteries after endothelial denudation. The genetically modified mice were also fed a high-fat high-cholesterol diet for 16 weeks for the determination of body weight gain, glucose and insulin levels, glucose tolerance and insulin secretion. Additionally, adipose tissue inflammation was assessed by analysis of adipose gene expression, and atherosclerosis was characterized by measuring fatty lesion size in the whole aorta, as well as in the aortic roots. Results: The results showed that whereas the expression of either splice variant is sufficient to impede denudation-induced fibrotic neointima formation and complex necrotic atherosclerotic lesions, the expression of the apoER2 splice variant containing exon 19 is necessary for the complete protection of injury-induced neointima formation in the vessel wall. However, exclusive expression of either apoER2 cytoplasmic splice variant does not influence the early phase of atherogenesis. Additionally, the exclusive expression of apoER2 without exon 19 promotes adipocyte inflammation and accelerates diet-induced insulin resistance and glucose intolerance. Conclusions: These results indicate that the apoER2 cytoplasmic variants have distinct and cell type-specific roles in influencing cardiometabolic disease development. Full article

Cardiac dysfunction is a severe complication of sepsis that significantly increases mortality in affected patients. Previous studies have shown better myocardial responses with preserved cardiac function in female animals compared to males following lipopolysaccharide (LPS)-induced sepsis. Our published findings have revealed that females exhibited less cardiac dysfunction than males when exposed to equivalent doses of tumor necrosis factor (TNF)α, which is markedly elevated in both heart tissue and serum following LPS. These raise the question of whether the observed sex differences in LPS-induced myocardial dysfunction are a direct effect of LPS or a secondary consequence mediated by inflammatory cytokines, like TNFα. In this study, we aimed to uncover sex differences in LPS-caused direct effects on cardiac function. To do so, isolated hearts from aged-matched adult male and female mice were subjected to LPS infusion using a Langendorff method. Left ventricular developed pressure (LVDP) was continuously recorded. The female estrous cycle was determined via vaginal smear. The oxidative phosphorylation (OXPHOS) pathway and estrogen receptors (ERs) were determined in heart tissue using Western blot. We found that males exhibited worse LV function than females following the infusion of LPS at 5.0 mg/kg body weight. However, no significant differences in cardiac function and expression of ERs were observed between female groups at different estrous stages. Interestingly, LV function returned to baseline after the initial depression of LVDP during the rapid response to LPS and then depressed again following the 50 min LPS infusion. Protein levels of OXPHOS were altered differently between male and female hearts after 50 min LPS infusion. Our data demonstrate that male hearts exhibit higher sensitivity to LPS-induced rapid cardiac dysfunction compared to females, although estrogen may have a minimal influence on LPS-induced rapid functional depression. Sex differences may exist in myocardial mitochondrial responses to direct LPS insult via the OXPHOS pathway. Full article

Background/Objectives: Breast cancer (BC) is the most commonly diagnosed cancer worldwide. Estrogen receptor (ER) status is a key determinant in the diagnosis and treatment of BC. Although immunohistochemistry (IHC) is the gold standard for ER assessment, it has limitations. This umbrella review aims to evaluate the role of 16α-18F-fluoro-17β-estradiol ([¹⁸F]FES) PET/CT as a non-invasive imaging tool for assessing ER expression and its implications in BC management. Methods: A comprehensive search was conducted in PubMed/MEDLINE and Cochrane Library for systematic reviews and meta-analyses published in the last decade. Studies eligible for inclusion evaluated the diagnostic accuracy and clinical utility of [¹⁸F]FES PET/CT in BC based on a predefined research question “What is the role of fluoroestradiol ([¹⁸F]FES) PET/CT in breast cancer?”. Data extraction and quality assessment were performed independently by two reviewers using the AMSTAR-2 tool. Results: Eight systematic reviews met the inclusion criteria. [¹⁸F]FES PET/CT demonstrated high sensitivity (81–94%) and specificity (78–95%) in detecting ER-positive lesions. It provided a real-time, whole-body assessment of ER expression, outperforming IHC in detecting functional ER activity. Additionally, [¹⁸F]FES PET/CT showed promise in predicting treatment response and guiding therapy decisions, particularly in metastatic settings. Conclusions: This review highlights the clinical value of [¹⁸F]FES PET/CT in BC management, offering a non-invasive alternative for ER assessment with high diagnostic accuracy. Its integration into clinical practice may enhance personalized treatment strategies for BC patients. Full article

Background: Breast cancer is a complex and heterogeneous disease characterized by distinct molecular subtypes with varying prognoses and treatment responses. Multiple factors influence breast cancer outcomes including tumor biology, patient characteristics, and treatment modalities. Demographic factors such as age, race/ethnicity, menopausal status, and body mass index have been correlated with variations in incidence, mortality, and survival rates. Over the past decade, comprehensive genomic profiling has been widely used to identify molecular biomarkers and signatures to develop novel therapeutic strategies for patients. For instance, the FLEX registry (NCT03053193) enrolled stage I–III breast cancer patients across 90 institutions in the United States and stratified risk groups based on a 70-gene signature (MammaPrint^®-MP) and molecular subtype based on an 80-gene signature (BluePrint^®-BP). This study aimed to identify the gene expression patterns and biomarkers associated with breast cancer risk and progression by integrating transcriptomic and clinical data. Methods: Targeted 111 unique gene expression and clinical data points from 978 breast cancer samples, representing each BP subtype (26% Luminal A, 26% Luminal B, 25% Basal, 23% HER2), obtained from Agendia Inc. These genes were selected based on their involvement in the mercapturic acid pathway, white and brown adipose tissue markers, inflammation markers, tumor-associated genes, apoptosis, autophagy, and ER stress markers. All statistical analyses, including principal component analysis (PCA), were performed using R version [4.4.0]. Prognostic values and genetic alterations were investigated using various web-based programs as described in the Methods section. Results: PCA of gene expression data revealed distinct clustering patterns associated with risk categories and molecular subtypes, particularly with principal component 4 (PC4). Genes related to oxidative stress, autophagy, apoptosis, and histone modification showed altered expression across risk categories and molecular subtypes. Key differentially expressed genes included SOD2, KLK5, KLK7, IL8, GSTM1/2, GLI1, CBS, and IGF1. Pathway analysis highlighted the enrichment of processes related to autophagy, cellular stress response, apoptosis, glutathione metabolism, deacetylation, and oxidative stress in high-risk and basal-like tumors compared with Ultralow and Luminal A tumors, respectively. Conclusions: This study identified gene expression signatures associated with breast cancer risk and molecular subtypes. These findings provide insights into the biological processes that may drive breast cancer progression and could inform the development of prognostic biomarkers and personalized therapeutic strategies. Full article

Background/Objectives: Trefoil factor protein 3 (Tff3) is a small peptide known as an epithelial tissue-protective protein, and it is also identified as a novel participant in complex metabolic processes. In numerous mouse models of obesity, Tff3 has been found to be downregulated in the liver and its overexpression is associated with an improvement in metabolic parameters. These mouse models with metabolic phenotypes have a multigenic background, with numerous genes contributing to their phenotype. To elucidate the role of Tff3 protein in metabolic events, we developed a mouse model with Tff3 deficiency on a C57Bl6N background without other intrinsic mutations affecting metabolism. Methods: We investigated the effects of a high-fat diet (9 weeks) on the liver of Tff3 protein-deficient mice of both sexes and the corresponding wild type. We investigated the general metabolic status of the animals and analysed the expression of markers of relevant pathophysiological pathways in the liver. Results:Tff3-deficient mice had significantly lower body weight. They also had a comparable total liver fat content but it was distributed in small vesicles, indicating the protective effect of Tff3 deficiency. The results of molecular analysis showed no major gene expression changes in inflammation-, ER- and oxidative stress-, and lipid metabolism-related genes. Tff3^−/− males had reduced expression of Il1α and Cxcr7 genes in the liver and no global proteome changes; Tff3-deficient females had decreased expression of Irs2 and Atf4 genes and total proteome comparison showed decreased levels of proteins related to ribosome biosynthesis and the inhibition of acetylation. Conclusions: Our results demonstrate that Tff3 deficiency reduces lipid accumulation in the liver and we set the direction for further studies aimed at uncovering the exact molecular mechanisms in other organs. Furthermore, it emphasises the need to include both sexes in future research, as the observed phenotype differs significantly depending on sex. Full article

Evaluating different tactics to mitigate the effects of gastrointestinal nematode infection in growing stocker cattle is essential to better understand opportunities to optimize cattle health and performance. Due to the potential development of anthelmintic resistance, parasitologists and industry stakeholders have proposed maintaining refugia in cattle populations and combination treatment as tactics to delay anthelmintic resistance yet limited large-scale field data are available for practitioners to make evidence-based decisions. The objective of this experiment was to compare the effects of extended-release eprinomectin injectable and doramectin injectable on growth and fecal shedding of parasites in stocker calves grazing with non-treated (refugia) cohorts. Steers (n = 995; 243.38 kg) were randomized to one of two experimental treatment groups on Day 0, extended-release eprinomectin (ERE) or doramectin injectable (DOR). A subset of animals (n = 47) was selectively not treated with an anthelmintic to maintain refugia (REF). Individual body weights were recorded on days 0, 105, and 130 to calculate average daily gain and overall body weight gain during each of those time periods. Fecal samples were collected per rectum from approximately 10% of the same animals in each group on days 0, 105, and 130. Mean fecal egg count was significantly lower in the 10% of animals tested in the ERE group on days 105 and 130 when compared to 10% of the animals in the DOR group (Day 105—ERE: 46.45 eggs per gram, DOR: 155.30 eggs per gram, p < 0.01; Day 130—ERE: 9.65 eggs per gram, DOR: 22.51 eggs per gram, p = 0.02). From day 0 to 105, the mean average daily gain in the ERE group was 0.87 kg/day, which tended (p = 0.055) to be higher than the mean for the DOR group, 0.845 kg/day. Full article

The aim of this research was to investigate the effects of primarily asymmetrical (soccer and volleyball) and symmetrical sport load (sprint and swimming) in the upper and lower limbs on dynamic balance and muscle strength and to compare these values in the dominant and non-dominant limbs. This study employed a cross-sectional design, included 45 adolescent female athletes from four sports, divided into asymmetric (ASYM, n = 25) and symmetric (SYM, n = 20) groups. They were assessed for maximal voluntary isometric muscle contraction (MVIC) relative muscular strength using a handheld dynamometer (HHD) for shoulder external rotation (ER) and internal rotation (IR), as well as hamstring and quadricep strength. Upper and lower limb balance were also assessed using the Upper (YBT-UQ) and Lower Quarter Y Balance Test (YBT-LQ) tests. The results showed significantly greater balance in the upper extremities of swimmers and in the lower extremities of the sprinters in both the dominant (DS) and non-dominant (NDS) sides than in other groups (p < 0.0001). However, no significant difference in internal and external shoulder rotator muscles strength between the groups (p > 0.05). Although significant differences were found in hamstring strength on the dominant side and quadricep strength on both sides (p < 0.05), a notable finding was that sprint athletes consistently demonstrated stronger quadriceps muscles as compared to other groups in both the dominant and non-dominant sides. According to the current findings, there are significant differences in upper and lower body balance, hamstring, and quadricep muscle strength among sports. This suggests that athletes of asymmetrical sports may need to improve non-dominant side knee strength and balance symmetry to prevent the risk of injury. Full article

Vincristine (VCR) is a chemotherapeutic agent classified as a vinca alkaloid. Royal jelly (RJ) is a significant bee product produced by worker bees, characterized by its high protein content. This study aims to investigate the protective effects of RJ against VCR-induced liver damage. VCR was intraperitoneally administered at a dose of 0.1 mg/kg body weight (b.w.) and RJ was orally administered at doses of 150 and 300 mg/kg b.w. Both treatments were applied to the rats on days 1–6 and 9–14. The composition of RJ was analyzed using LC-MS/MS, revealing the presence of 15 different phytochemical compounds with strong antioxidant properties. Serum samples obtained from the rats were analyzed for ALT, ALP, and AST levels. While these enzyme levels were significantly elevated in the VCR group, a notable reduction was observed following RJ administration. Additionally, SOD, CAT, GPx, and GSH antioxidant parameters, along with MDA levels, were evaluated in liver tissue samples. The results indicated a decrease in SOD, CAT, GPx, and GSH activities/levels and an increase in MDA levels in the VCR group. Furthermore, ELISA was used to assess JAK2, STAT3, and mTOR/PI3K/AKT signaling pathways. VCR administration led to a decrease in mTOR/PI3K/AKT levels and an increase in JAK2 and STAT3 levels. In addition, the mRNA transcription levels of inflammation (NF-κB, TNF-α, and IL-1β), endoplasmic reticulum (ER) stress (IRE-1, GRP78, PERK, and ATF-6), and autophagy markers (LC3A and LC3B) were examined. A significant increase in inflammation, ER stress, and autophagy-related markers was observed in the VCR-treated group. Lastly, the protein expression levels of Bax, Bcl-2, Caspase-3, and NF-κB were evaluated. VCR treatment increased Bax, Caspase 3, and NF-κB levels, whereas Bcl-2 levels were decreased. However, following RJ administration, all these parameters were reversed, demonstrating significant improvements. In conclusion, these findings suggest that RJ may exert a protective effect against VCR-induced liver damage. Full article

The Luhai uranium deposit is a large-scale uranium deposit newly discovered in recent years through comprehensive prospecting methods. It is located in the Basaiqi Paleochannel Uranium metallogenic belt of the Erlian Basin and is characterized by its shallow burial and large scale. This paper provides new data on the genetic processes of sandstone-type uranium mineralization through sedimentological and geochemical environmental indicators (such as Fe³⁺/Fe²⁺, organic carbon, total sulfur, etc.), analysis of C-O isotopes of carbonate cements and H-O isotopes of groundwater, and geochemical and mineralogical studies of uranium minerals, iron–titanium oxides (involving backscatter analysis, micro-area chemical composition determination, and elemental surface scanning), and organic matter. Sedimentological analysis shows that the ore- bearing layer in the upper member of the Saihan Formation developed a braided channel within floodplain subfacies, which control the distribution of uranium ore bodies. Uranium mineralogical observations, geochemical environmental indicators, and organic geochemical data indicate that the main reducing agents related to mineralization are pyrite, terrestrial plants, and deep-sourced oil and gas. The δD values of groundwater in the ore-bearing layer range from −95.34‰ to −90.68‰, and the δ¹⁸O values range from −12.24‰ to −11.87‰. For calcite cements, the δ¹⁸O_V-PDB values range from −24‰ to −11.5‰, and the δ¹⁸_OV-SMOW values range from 6.2‰ to 19‰. It was determined that the ore-forming fluid is mainly surface fresh water that entered the strata during the tectonic uplift stage, with local mixing of deep-sourced brine. Based on these data, the main modes of uranium mineralization in the paleochannel were obtained as follows: (1) Redox mineralization occurs due to the reducing medium within the sand body itself and the reduction caused by deep- sourced oil and gas generated from the Tengge’er and Arshan Formations. (2) Mineralization is achieved through the mixing of fluids from different sources. Furthermore, a genetic model related to uranium mineralization in the paleochannels of the Luhai area has been established: favorable uranium reservoirs were formed during the sedimentary period, and during the post-sedimentary stage, reverse structures promoted redox reactions and fluid-mixing-induced mineralization. The research findings can provide guidance for the exploration of paleochannel sandstone-type uranium deposits in other areas of the Erlian Basin. Full article

The liver plays a crucial role in maintaining lipid homeostasis by converting toxic free fatty acids into VLDL, which the body uses for energy. Even minor changes in VLDL formation and secretion can result in serious health conditions such as atherosclerosis and non-alcoholic fatty liver disease. Despite the importance of VLDL, the proteins and signaling pathways involved in its regulation remain largely unknown. This study aims to develop a novel methodology to study intracellular VLDL transport events and explore the role of liver fatty acid-binding protein (LFABP) in VLDL transport and secretion. Current methods to study VLDL are often tedious, time-consuming, and expensive, underscoring the need for an alternative approach. We designed a new immunofluorescence-based assay to track the formation and secretion of VLDL in cells over time using fluorescently tagged TopFluor oleic acid. Confocal microscopy confirmed that TopFluor oleic acid enters hepatocytes and colocalizes with the ER, Golgi, and plasma membrane. Additionally, the collection of cell culture media revealed that TopFluor was incorporated into VLDL particles, as confirmed by fluorescence readings and ApoB100 immunoblots. This novel assay provides a valuable tool for further research into the mechanisms of VLDL regulation and the development of potential therapeutic targets for related diseases. Utilizing this assay, we identified LFABP as a key regulatory protein in post-Golgi VLDL trafficking. Our data suggest that LFABP plays a crucial role in this process, and its functional impairment leads to reduced VLDL secretion. Full article

Metabolic syndrome (MetS) constitutes a spectrum of interconnected conditions comprising obesity, dyslipidemia, hypertension, and insulin resistance (IR). While a singular, all-encompassing treatment for MetS remains elusive, an integrative approach involving tailored lifestyle modifications and emerging functional food therapies holds promise in preventing its multifaceted manifestations. Our main objective was to scrutinize the efficacy of cranberry proanthocyanidins (PAC, 200 mg/kg/day for 12 weeks) in mitigating MetS pathophysiology in male mice subjected to standard Chow or high-fat/high-fructose (HFHF) diets while unravelling intricate mechanisms. The administration of PAC, in conjunction with an HFHF diet, significantly averted obesity, evidenced by reductions in body weight, adiposity across various fat depots, and adipocyte hypertrophy. Similarly, PAC prevented HFHF-induced hyperglycemia and hyperinsulinemia while also lessening IR. Furthermore, PAC proved effective in alleviating key risk factors associated with cardiovascular diseases by diminishing plasma saturated fatty acids, as well as levels of triglycerides, cholesterol, and non-HDL-C levels. The rise in adiponectin and drop in circulating levels of inflammatory markers showcased PAC’s protective role against inflammation. To better clarify the mechanisms behind PAC actions, gut–liver axis parameters were examined, showing significant enhancements in gut microbiota composition, microbiota-derived metabolites, and marked reductions in intestinal and hepatic inflammation, liver steatosis, and key biomarkers associated with endoplasmic reticulum (ER) stress and lipid metabolism. This study enhances our understanding of the complex mechanisms underlying the development of MetS and provides valuable insights into how PAC may alleviate cardiometabolic dysfunction in HFHF mice. Full article

Breast cancer is the most clinically relevant pathology of the mammary gland and is currently the most diagnosed malignant disease among women worldwide. In breast cancer prevention, it is important to consider that the risk of developing the disease is not the same for the entire population. This pathology presents heterogeneous clinical manifestations and the most common classification is related to the following hormonal receptors: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and triple-negative (TNBC). Currently, a new class of therapy is being used for cancer treatment: anti-body-drug conjugates. A bibliographic search was performed by establishing keywords and then combining them using Boolean operators OR and AND. Thus, the search equation was formulated according to the PICO search question to be used in the PubMed database. Results: Fifteen studies that met the established inclusion criteria were analyzed, and their methodological quality was assessed using the Joanna Briggs Institute approach, demonstrating high reliability in the results obtained, the analyzed studies focus on the combination of adjuvant Pertuzumab + Trastuzumab with chemotherapy for the treatment of HER2-positive breast cancer. Scientific evidence suggests that the combination of pertuzumab and trastuzumab not only improves the survival of patients with HER2-positive breast cancer but also provides a safe and flexible treatment option. Full article