Background Breast Cancer Research Articles

Meta-Analysis of Predictive Value of Ki-67 before Neoadjuvant Chemotherapy in Breast Cancer Patients

Abstract Background Breast cancer is the second most common malignancy among female patients. Early breast cancer is considered potentially curable. Immunohistochemistry has an important role in the pathology of breast disease. It is widely used to localize specifically proteins in cells and tissues. Ki-67, a marker of cell proliferation, is a specific nuclear antigen expressed in all phases of the cell cycle, which can be readily detected using immunohistochemistry methods. Many guidelines and international groups concluded that measurement of Ki-67 could be important both in standard clinical practice and within clinical trials. Objective To clarify relation between expression of Ki67 and response of malignant cells to neoadjuvant chemotherapy in breast cancer. Methods The search was directed through PubMed / MEDLINE, Scopes, Web of science, and the Cochrane Library for information from inception to July 1, 2022, with a combination of the following terms: “Ki-67”, “breast cancer” and “NCT”. More searches by Google Scholar have been used to supplement the search with the sites mentioned above. Abstract-based eligibility studies were obtained, and the manuscripts were fully reviewed. Report bibliographies that meet the eligibility criteria were reviewed for further studies. Results A recently published meta-analysis reported that a high Ki-67 level was associated with a high pCR rate. Our results demonstrate that patients with a Ki- 67 are more sensitive to NCT, have higher pCR rates, and benefit more from NCT compared to those with a low Ki-67. However, it remains unclear whether other factors such as therapy regimens and cycles of NCT, the clinical stage, and tumor location have an impact on Ki-67-based health outcomes. Conclusion The meta-analysis reported here demonstrates that pretherapeutic Ki-67 is associated with pCR in breast cancer patients undergoing neo-adjuvant chemotherapy.

Assessment of Use of Subcutaneous Mastectomy with Silicon Prostheses as Treatment of Early Breast Cancer

Abstract Background Breast cancer is the most common cancer among women and the second most common cause of cancer death in the United States. Approximately 268,600 new breast cancer diagnoses and 41,760 cancer- related deaths in the U.S. were estimated for 2019. SSM (skin sparing mastectomy) is defined as a simple or radical surgery with modified minimal incisions that retain the widest possible coverage and sub-cutaneous breast groove but dry the NAC, flaws of previous biopsies and/or scarring caused by diagnostic percutaneous biopsies. Access to the armpit for a possible sentinel-node biopsy or axillary dissection is obtained through the same incision. An additional incision may be necessary to perform the reconstructive procedure (e.g., microsurgical axillary anastomosis). Objective To study the risks and benefits of use subcutaneous mastectomy with silicon prosthesis as treatment of early breast cancer: as regards the impact of radiotherapy administration on implant, psychological impact, operative time and post-operative complications including complication of silicon, effect on wound healing. Patients and Methods This prospective interventional study was conducted at tertiary care hospital at the general surgery department in Ain Shams University hospitals and Misr University for Science and Technology (MUST) hospital and from November 2021, till July 2022 and performed on total 15 females suffering from stage I-II infiltrating breast carcinomas. Results The current study revealed that mean ±SD of age of the studied cases was 46.3±7.4. Regarding tumor site, LOQ was the most frequent (40.0%), followed by UIQ (33.3%), then UOQ (20.0%) and lastly LIQ (6.7%). Concerning T grades, T1 was in (46.7%), while the remaining (53.3%) were T2. Concerning N grades, N0 was in (73.3%), while the remaining (26.7%) were N1. Sentinel lymph nodes done in 73.3% of cases. As regards operative characteristics, Axillary clearance done in less than half of cases (46.7%), while nipple sparing achieved in less than quarter of cases (20.0%). As regards post-mastectomy treatment, majority of cases (86.7%) received hormonal therapy, adjuvant radiotherapy to axilla was (46.7%), chemotherapy (33.3%), while immunotherapy was (6.7%). As regards postoperative side effects, Pain was the most frequent postoperative side effect; detected in (33.3%) of cases, followed by seroma (20.0%), then flap necrosis (13.3%), and the least frequent was hematoma (6.7%). As regards postoperative patients’ satisfaction, mean ±SD of Postoperative patients’ satisfaction was 7.3±1.5 with range 5.0 − 10.0. Near half of the studied cases (46.7%) had 7.0 − 8.0 satisfaction grade. Conclusion Skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) with immediate subcutaneous silicon implantation are an acceptable and safe method for breast reconstruction. It offers a number of advantages including ease of dissection for surgeons, improved symmetry, and low complication rates. With improvements in surgical techniques in preserving mastectomy skin flap viability, the traditionally higher rates of complications in subcutaneous implants may be outdated. The present study can burden the knowledge and shed some light on future prospective studies with larger sample sizes to evaluate a cost benefit analysis and patient and surgeon assessment of outcomes to directly compare with traditional submuscular single- or 2- stage implant-based reconstruction.

Comparative Study between Pectoral Nerve Block Type-II (PECS II) and Serratus Anterior Plane Block (SAPB) in Postoperative Analgesic Efficacy in Modified Radical Mastectomy

Abstract Background Breast cancer is the most common cancer in women both in the developed and less developed world. In 2012, it represented about 12 percent of all new cancer cases and 25 percent of all cancers in women. Aim of the Work The aim of this work is to evaluate the efficacy of ultrasound guided pectoral nerve block type two versus Serratus Anterior plane block regarding postoperative pain control in patients undergoing modified radical mastectomy. Patients and Methods After obtaining approval from the medical ethical committee in Ain Shams University, this study was conducted in the operating theatres of Ain Shams University Hospitals. It included 70 female patients undergoing modified radical mastectomy were divided randomly into two groups, each group consisted of 35 patients; Group I patients received pectoral nerve block type two (PECS II), Group II patients received Serratus Anterior Plane Block (SAPB). Results The results of our study showed that there was no statistically significant difference between groups regarding demographic data. There was a statistically significant decrease in Mean blood pressure (mmHg) in Group I compared with Group II from hour-4 to hour-16 postoperative. However, a statistically significant decrease in group I compared to group II regarding postoperative heart rate (beat/min) from hour-4 to hour-16. A statistically significant decrease in group I compared to group II regarding visual analogue score for pain from minute-30 to after 12 hrs also was found. The current study shows highly statistically significant difference between groups as regard the need to intraoperative fentanyl incremental doses, time of first rescue analgesia, number of patients who received postoperative pethidine and total dose of opioids during the first 24 hrs. Conclusion Our findings suggest that PECS II block is more effective regarding postoperative pain control in patients undergoing modified radical mastectomy under general anesthesia compared to SAPB especially in the first 16 hours postoperative. Also patients underwent PECS II block show less need to intraoperative fentanyl incremental doses, less need to postoperative opioids and longer duration for time of rescue analgesia compared to patients underwent SAPB.

Retrospective Comparative Study between Results of Neo Adjuvant Chemotherapy and Upfront Surgery in Breast Cancer in Aswan Oncology Center

Abstract Background Breast cancer is a global health problem, with more than 1 million cases of breast cancer diagnosed worldwide each year. Introduction of neoadjuvant chemotherapy (NACT) has dramatically changed the management of breast cancer. Aim and Objectives To compare the clinicopathological features, surgical procedures, and outcome parameters of primary and post-neoadjuvant chemotherapy breast conseravtive surgery, with the aim of comparing the outcomes in terms of ipsilateral breast tumor recurrence rates and over all free survival in the two groups. Subjects and Methods This was a Comparative study, was conducted in Aswan oncology center on (40) women diagnosed with breast cancer, divided into two groups: (Group A): 20 up front surgery patients then adjuvant chemoherapy, (Group B): 20 Neo adjuvant chemotherapy then surgery patients during 6 months. Result There was statistically significant difference between the two studied groups as regard Metastatic work up and local recurrence. Conclusion The neoadjuvant chemotherapy has a nearby significant impact on pathological complete response (PCR) in patients with breast cancer with no significant increased toxicity and has significant lower rates of metastasis compared to upfront surgery.Neoadjuvant chemotherapy followed by surgery is a safe and effective rather than conventional method (primary surgery followed by Adjuvant chemotherapy) in treatment of Breast cancer.

Net costs of breast cancer in Colombia: a cost-of-illness study based on administrative claims databases

BackgroundBreast Cancer (BC) is associated with substantial costs of healthcare; however, real-world data regarding these costs in Colombia is scarce. The contributory regime provides healthcare services to formal workers and their dependents and covers almost half of the population in Colombia. This study aims to describe the net costs of healthcare in women with BC covered by the contributory regime in Colombia in 2019 from the perspective of the Colombian Health System.MethodsThe main data source was the Capitation Sufficiency Database, an administrative database that contains patient-level data on consumption of services included in the National Formulary (PBS, in Spanish Plan de Beneficios en Salud). Data on consumption of services not included in the PBS (non-PBS) were calculated using aggregated data from MIPRES database. All direct costs incurred by prevalent cases of BC, from January 1 to December 31, 2019, were included in the analysis. The net costs of the disease were estimated by multiplying the marginal cost and the expected number of cases with BC by region and age group. Marginal costs were defined as the costs of services delivered to patients with BC after subtracting the expected costs of health services due to age, comorbidity burden or region of residence. To calculate these costs, we used Propensity Score Matching in the main analysis. All costs were expressed in 2019 international dollars. Productivity losses, transportation expenses, and caregiving costs were not included.ResultsA total of 46,148 patients with BC were identified. Total net costs were $387 million (95% CI $377 to $396 million), 60% associated with non-PBS services. Marginal costs were $8,366 (95% Confidence Interval $8,170 to $8,573), with substantial variations between regions age groups (from $3,919 for older patients in the Amazonia region to $10,070 for younger patients in the Pacific region). The costs for PBS services were higher for ambulatory services and for patients who died during 2020.ConclusionsBC imposes a substantial economic burden for the Colombian Health System with important variations in net costs between regions and age groups. Patients near death and ambulatory services were associated with higher costs of healthcare.

The mechanism and therapeutic potential of lncRNA MIR497HG/miR-16-5p axis in breast cancer

BackgroundBreast cancer has become a major public health problem in the current society, and its incidence rate ranks the first among Chinese female malignant tumors. This paper once again confirmed the efficacy of lncRNA in tumor regulation by introducing the mechanism of the diagnosis of breast cancer by the MIR497HG/miR-16-5p axis.MethodsThe abnormal expression of MIR497HG in breast cancer was determined by RT-qPCR method, and the correlation between MIR497HG expression and clinicopathological characteristics of breast cancer patients was analyzed via Chi-square test. To understand the diagnostic potential of MIR497HG in breast cancer by drawing the receiver operating characteristic curve (ROC). The overexpressed MIR497HG (pcDNA3.1-MIR497HG) was designed and constructed to explore the regulation of elevated MIR497HG on biological function of BT549 and Hs 578T cells through Transwell assays. Additionally, the luciferase gene reporter assay and Pearson analysis evaluated the targeting relationship of MIR497HG to miR-16-5p.ResultsMIR497HG was decreased in breast cancer and had high diagnostic function, while elevated MIR497HG inhibited the migration and invasion of BT549 and Hs 578T cells. In terms of functional mechanism, miR-16-5p was the target of MIR497HG, and MIR497HG reversely regulated the miR-16-5p. miR-16-5p mimic reversed the effects of upregulated MIR497HG on cell biological function.ConclusionsIn general, MIR497HG was decreased in breast cancer, and the MIR497HG/miR-16-5p axis regulated breast cancer tumorigenesis, providing effective insights for the diagnosis of patients.

Antitumor, antioxidant, and anti-inflammatory activity of spirulina against 7,12-dimethylbenzanthracene-induced mammary cancer

Background Breast cancer is the most abundant malignancies worldwide; however, its current therapies encounter drug resistance or exhibit numerous side effects. Marine and freshwater algal biomasses, such as spirulina, are rich with many biological active components. Objective The main objective of the current study was to investigate the therapeutic, antioxidant, and immune-modulating efficiency of spirulina on breast tumor modelled female rats, especially through the inhibition of the phosphoinositide 3-kinases/Akt/mammalian target of rapamycin pathway. Materials and methods 7,12-dimethylbenzanthracene (DMBA)-induced mammary cancer rats were ingested with spirulina (500 mg/kg/day) for 6 weeks, then blood and tissue samples of normal and spirulina-treated cancer rats were obtained and tested for biochemical, immunological, and histopathological assessments. Cancer model is used in this experiment. Results The results showed that spirulina is rich in phenolic compounds that have high scavenger activity and reducing power reflecting the antioxidant potential of spirulina. Treatment of DMBA-induced mammary cancer rats with spirulina resulted in improvement in mammary oxidative stress status that was distorted due to DMBA administration; meanwhile, superoxide dismutase, glutathione peroxidase, and reduced glutathione values were elevated significantly coupled with a marked drop in nitric oxide and malondialdehyde levels. In addition, spirulina boosts the immune-modulating response against tumor as the serum proinflammatory cytokines (tumor necrosis factor alpha, interlukin-1 beta, and interlukin-6) were markedly downregulated, and associated with inhibition of Akt and mammalian target of rapamycin pathway; this in turn suppress the tumor proliferation and progression. Furthermore, the prognosis of the treatment was indicated by the clear reduction of serum cancer antigen 15.3 level accompanied by elevation in serum level of the apoptotic biomarkers (caspase-3 and CD4) inferring the upregulation of tumor suppressor genes. Similarly, spirulina ameliorated lipid profile and the biochemical markers of hepatorenal functions (alanine transaminase, aspartate transaminase, urea, and creatinine) that were disturbed by DMBA; therefore, it has a positive impact on the body health. These biochemical improvements were associated with a notable improvement in the histological architecture of the mammary tissue. Conclusion In conclusion, spirulina has proved considerable antitumor, antioxidant, and anti-inflammatory activities against DMBA-induced mammary cancer.

Comparative Evaluation of USG-Guided Single Tissue Marker Versus Multiple Tissue Marker Placements in Breast Malignancy Patients Undergoing Neoadjuvant Chemotherapy for Tumor Localization.

Background Breast cancer remains one of the most common malignancies affecting women globally, contributing significantly to the disease burden. The advent of neoadjuvant chemotherapy (NAC) has revolutionized the treatment for locally advanced breast cancer, allowing tumors to be downstaged and making breast-conserving surgery (BCS) feasible. Accurate localization of the tumor bed post-NAC is crucial for successful surgical removal of residual disease. While traditional single tissue marker placement has been effective, recent advances suggest multiple markers might provide superior localization by comprehensively delineating the entire tumor area. This study aims to compare the effectiveness of single versus multiple tissue marker placements in breast malignancy patients undergoing NAC. Materials and methods A prospective study was conducted in the Department of Radio-diagnosis at Saveetha Medical College over 18 months, including 10 patients diagnosed with breast carcinoma, selected through convenience sampling. Inclusion criteria involved patients diagnosed with breast cancer via mammography, sonography, and histological confirmation, referred for clip placement before NAC. Exclusion criteria were patients unwilling to participate. The procedure involved placing one to two surgical clips within the tumor using a 14/16-gauge coaxial guiding needle under USGguidance, with additional clips for larger or multiple tumors. Data collection included pre-procedural USG, post-procedural mammography (MG1), pre-operative mammography (MG2)/USG, and gross specimen histopathological examination/specimen mammography. Statistical analysis Demographic data, clipping distribution, receptor status, localization methods, surgical outcomes, operation diagnoses, and correlation analysis were statistically analyzed. Mean age, standard deviation, and p-values were calculated to determine the significance of differences between single and multiple clip groups. Results The study included 10 patients with a mean age of 52.5 years. Of these, five (50%)had a single clip, and two (20%)had four clips. The average time from clipping to the second mammogram (MG2) was 106.3 days, and from clipping to operation was 111.0 days, with longer follow-up times for multiple clip patients. Six (60%) of the patients were estrogen receptor (ER) positive, and six (60%) were human epidermal growth factor receptor 2 (HER2) negative. Localization methods were similar between single and multiple clip groups. However, multiple clip patients tended to undergo more extensive surgeries like modified radical mastectomy (MRM). Imaging responses showed no preoperative ultrasound lesions in single clip patients, while multiple clip patients had higher inconsistent diagnoses (10 (100%)) suggesting that multiple clips provide better tumor localization but are linked to increased complexity and longer follow-up times. Conclusion Patients with multiple clips experienced significantly longer follow-up times, reflecting more complex clinical scenarios. Despite no significant differences in receptor status distributions, multiple clip patients required more extensive surgeries, emphasizing the need for tailored surgical planning. The study underscores the importance of considering the number of clips in clinical decision-making. Future research should focus on larger, prospective studies to validate these findings and explore underlying mechanisms.

The effectiveness of semi-wild Sumatran mango (Mangifera spp.) leaves as a phytotherapy agent for breast cancer

Background Breast cancer ranks first in the world, standing at a mortality rate of 24.5% per year and is the leading cause of cancer death in Indonesia. The current management of breast cancer therapy is considered less effective because of its careful use due to side effects that are detrimental to the patient. The semi-wild species from Sumatra are neglected and underutilized species but have the potential as a therapeutic agent. Previous research has revealed that this species of mango is high in antioxidant compounds. Objective This study was carried out to discover the anticancer activities of the semi-wild mango species via inhibitory activities and morphological changes in Michigan Cancer Foundation-7 (MCF-7) cells. Materials and methods The IC50 value of Mangifera sumatrana, Mangifera foetida, and Mangifera laurina leaves in n-hexane, ethyl-acetate, and methanol extracts was determined using the reagent 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Data were analyzed by two-way analysis of variance using IBM SPSS Statistics 21. Results and conclusion M. laurina n-hexane extracts exhibited anticancer activity (IC50 13.25 ppm). Nonpolar solutions were chosen as the most effective extraction solvent in anticancer tests because lipids in nonpolar solvents can hit the lipid bilayer. A hexane fraction was created by separating the majority of nonpolar fatty acid esters, and this fraction had a considerable impact on cytotoxic and apoptotic effects on MCF-7 cells. Therefore, all treatments can transform MCF-7 cells’ morphology into blackened dead cells that are degraded into small parts, such as apoptotic bodies in cells undergoing apoptotic processes. MTT assays against MCF-7 on three species of semi-wild Sumatran mango in different extraction solvents showed that n-hexane extracts of M. laurina had stronger anticancer activity than other samples. This study provides new information to support the development of standardized herbal medicines and phytopharmaca in the future.

Exploring the feasibility and implications of cranioencephalic computed tomography in HER2-positive breast cancer: A pilot study

BackgroundBreast cancer has several subtypes, including HER2-positive breast cancer, which is characterized by overexpression of human epidermal growth factor receptor 2 (HER2), aggressiveness, poor prognosis, and high risk of recurrence and metastasis. Brain metastases are a common complication of HER2-positive breast cancer, but brain imaging is not included in the initial staging of this disease. This prospective pilot study aimed to evaluate the usefulness of brain computed tomography (CT) in the initial staging of HER2-positive breast cancer. Patients and methodsFifty-eight patients were enrolled and demographic, clinical, and breast cancer-specific data were collected after the informed consent and ethical approval were obtained. ResultsA descriptive analysis was performed. The median age of the patients was 55 years, and the majority had good performance status. Brain CT scans were performed at diagnosis, and no brain metastases were detected in early-stage patients. However, brain CT identified brain metastases in one advanced-stage patient with clinical suspicion. ConclusionsThis study suggests that brain CT may have limited utility in the initial staging of early HER2-positive breast cancer, while it could be a valuable tool in advanced cases. Further research is needed, including a higher number of patients to identify those with high risk, which may benefit from brain imaging.

Retrospective evaluation of the contribution of radiotherapy to survival in breast cancer treatment with propensity score based on stage and subgroup

BackgroundBreast cancer has been a disease in which treatment strategy has changed over time under the influence of different hypotheses and evidence for more than a century. We analyzed the contribution of radiotherapy to disease-free survival and overall survival by classifying according to stage, 1–3 lymph node involvement, and molecular subgroups.MethodsFollowing the approval of the Institutional Review Board, records of patients with breast cancer who were admitted to University School of Medicine Departments of Radiation Oncology and Medical Oncology between July 1999 and December 2020 were reviewed. Using data propensity score matching was performed between the groups that did and did not receive radiotherapy using an optimal matching algorithm (optimum, 1:1). Disease-free survival and overall survival after propensity score matching were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis was used to estimate hazard ratios.ResultsIn the radiotherapy and non-radiotherapy groups, disease-free survival was 257.42 ± 5.46 (246.72- 268.13), 208,96 ± 8,15 (192,97–224,94) months respectively, (p = < 0.001), overall survival was 272,46 ± 8,68 (255,43–289,49), 219,05 ± 7,32 (204,70–233,41) months respectively (p = .002). We compared the 19 N1 patient groups who received radiotherapy with the 19 patients who did not receive radiotherapy and calculated the disease-free survival times was 202,21 ± 10,50 (181,62–222,79) and 148,82 ± 24,91 (99,99–197,65) months respectively (p = .011) and overall survival times was 200,85 ± 12,79 (175,77–225,92) and 166,90 ± 20,39 (126,93–206,82) months respectively (p = .055). We examined disease-free survival and overall survival times in both groups according to Luminal A, Luminal B, TNBC, and HER2-enriched subgroups. In the Luminal B subgroup, the disease-free survival duration in the groups receiving radiotherapy and not receiving radiotherapy was 264.83 ± 4.95 (255.13-274.54) and 187.09 ± 11.06 (165.41-208.78) months (p < .001), and overall survival times were 252.29 ± 10.54 (231.62-272.97) and 197.74 ± 9.72 (178.69–216.80) months (p = .001) respectively.ConclusionsThanks to studies proving that RT increases long-term survival rates in breast cancer as a result of reducing locoregional recurrence and systemic metastasis rates, it has been understood that the spectrum hypothesis is the hypothesis that most accurately describes breast cancer to date. We found that patients with Luminal B invasive breast cancer benefited significantly more from RT compared to other subgroups.

Computed tomography-based structural rigidity analysis can assess tumor- and treatment-induced changes in rat bones with metastatic lesions

BackgroundBreast cancer (BrCa) is a predominant malignancy, with metastasis occurring in one in eight patients, nearly half of which target the bone, leading to serious complications such as pain, fractures, and compromised mobility. Structural rigidity, crucial for bone strength, becomes compromised with osteolytic lesions, highlighting the vulnerability and increased fracture risk in affected areas. Historically, two-dimensional radiographs have been employed to predict these fracture risks; however, their limitations in capturing the three-dimensional structural and material changes in bone have raised concerns. Recent advances in CT-based Structural Rigidity Analysis (CTRA), offer a promising, more accurate non-invasive 3D approach. This study aims to assess the efficacy of CTRA in monitoring osteolytic lesions’ progression and response to therapy, suggesting its potential superiority over existing methodologies in guiding treatment strategies.MethodsTwenty-seven female nude rats underwent femoral intra-medullary inoculation with MDA-MB-231 human breast cancer cells or saline control. They were divided into Control, Cancer Control, Ibandronate, and Paclitaxel groups. Osteolytic progression was monitored weekly using biplanar radiography, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DEXA). CTRA was employed to predict fracture risk, normalized using the contralateral femur. Statistical analyses, including Kruskal-Wallis and ANOVA, assessed differences in outcomes among groups and over time.ResultsBiplanar radiographs showed treatment benefits over time; however, only certain time-specific differences between the Control and other treatment groups were discernible. Notably, observer subjectivity in X-ray scoring became evident, with significant inter-operator variations. DEXA measurements for metaphyseal Bone Mineral Content (BMC) did not exhibit notable differences between groups. Although diaphyseal BMC highlighted some variance, it did not reveal significant differences between treatments at specific time points, suggesting a limited ability for DEXA to differentiate between treatment effects. In contrast, the CTRA consistently demonstrated variations across different treatments, effectively capturing bone rigidity changes over time, and the axial- (EA), bending- (EI), and torsional rigidity (GJ) outcomes from the CTRA method successfully distinguished differences among treatments at specific time points.ConclusionTraditional approaches, such as biplanar radiographs and DEXA, have exhibited inherent limitations, notably observer bias and time-specific inefficacies. Our study accentuates the capability of CTRA in capturing real-time, progressive changes in bone structure, with the potential to predict fractures more accurately and provide a more objective analysis. Ultimately, this innovative approach may bridge the existing gap in clinical guidelines, ushering in enhanced Clinical Decision Support Tool (CDST) for both surgical and non-surgical treatments.

Synthesis of metformin-derived fluorescent quantum dots: uptake, cytotoxicity, and inhibition in human breast cancer cells through autophagy pathway

BackgroundBreast cancer remains a challenge for physicians. Metformin, an antidiabetic drug, show promising anticancer properties against cancers. An emerging quantum dot (QD) material improves therapeutic agents’ anticancer and imaging properties. QD are nano-sized particles with extreme application in nanotechnology captured by cells and accumulated inside cells, suggesting bioimaging and effective anticancer outcomes. In this study, a simple one-pot hydrothermal method was used to synthesize fluorescent metformin-derived carbon dots (M-CDs) and then investigated the cytotoxic effects and imaging features on two human breast cancer cell lines including, MCF-7 and MDA-MB-231 cells.ResultsResults showed that M-CDs profoundly decreased the viability of both cancer cells. IC50 values showed that M-CDs were more cytotoxic than metformin either 24–48 h post-treatment. Cancer cells uptake M-CDs successfully, which causes morphological changes in cells and increased levels of intracellular ROS. The number of Oil Red O-positive cells and the expression of caspase-3 protein were increased in M-CDs treated cells. Authophagic factors including, AMPK, mTOR, and P62 were down-regulated, while p-AMPK, Becline-1, LC3 I, and LC3 II were up-regulated in M-CDs treated cells. Finally, M-CDs caused a decrease in the wound healing rate of cells.ConclusionsFor the first, M-CDs were synthesized by simple one-pot hydrothermal treatment without further purification. M-CDs inhibited both breast cancer cells through modulating autophagy signalling.Graphical

ZNF623 contributes to breast carcinoma progress by recruiting CtBP1 to regulate NF-κB pathway

BackgroundBreast cancer ranks among the most prevalent tumor types worldwide. Copy number amplification of chromosome 8q24 is frequently detected in breast cancer. ZNF623 is a relatively unexplored gene mapped to 8q24. Here, we explore the expression profile, prognostic significance, and biological action of ZNF623 in breast carcinogenesis. MethodsTo evaluate the mRNA expression pattern and prognostic relevance of ZNF623 across different cancer types, we conducted bioinformatic analyses. The expression of the gene was suppressed using ZNF623 shRNAs/siRNAs and augmented through transfection with plasmids containing ZNF623 cDNA. Cell viability assay, clonogenic assay, and transwell migration assay were utilized to assess the proliferation, viability, and invasion capacity of breast cancer cell lines. Luciferase reporter assay served as a pivotal tool to ascertain the transcriptional activity of ZNF623. IP-MS and co-IP were employed to validate that ZNF623 interacted with CtBP1. ChIP analysis and ChIP-qPCR were conducted to assess the genes targeted by ZNF623/CtBP1 complex. Flow cytometry was conducted to evaluate the phosphorylation status of p65. ResultsZNF623 expression was notably elevated in breast cancer (BC). Prognostic analysis indicated higher expression of ZNF623 indicated worse survival. Functional experiments discovered that the upregulation of ZNF623 significantly enhanced both the proliferative and migratory capacities of breast cancer cells. Luciferase reporter assay indicated that ZNF623 was a transcription repressor. Immunoprecipitation coupled mass spectrometry analysis revealed a physical association between ZNF623 and CtBP1 in the interaction group. The conjoint analysis of ChIP-seq and TCGA DEG analysis revealed that the ZNF623/CtBP1 complex repressed a series of genes, such as negative regulation of the NF-kappaB signaling pathway. Flow cytometry analysis discovered that knockdown of ZNF623 decreased the phosphorylation level of p65, indicating that ZNF623 could regulate the activity of the NF-κB pathway. ConclusionZNF623 predicts poor prognosis of BC and enhances breast cancer growth and metastasis. By recruiting CtBP1, ZNF623 could suppress NF-κB inhibitors, including COMMD1, NFKBIL1, PYCARD, and BRMS1, expression from the transcription level.

In-vitro study of cytotoxic and apoptotic potential of Thalassia hemprichii (Ehren.) Asch. And Enhalus acoroides (L.f.) Royle against human breast cancer cell line (MCF-7) with correlation to their chemical profile

BackgroundBreast cancer is the most common type of cancer diagnosed in women. Finding novel therapeutic agents with significant cytotoxic action and minimal adverse impact on normal cells becomes crucial. Today, natural anticancer agents present an unconventional method of treating cancer, either as a curative or preventative agent, with considerable concern for marine organisms.MethodsThe anticancer effect of the alcoholic extract of different Red Sea Seagrasses on MCF-7 human breast cancer cell line has been investigated. Seagrasses were collected from Wadi El Gamal, Red Sea and extracted. Qualitative HPLC analysis was performed on the extracts for the identification of their active biomarkers. This study was aimed to explore the cytotoxic impact of Thalassia hemprichii (Ehren.) and Enhalus acoroides (L.f.) Royle on MCF-7 and their mode of action. Their anti-proliferative effects on cancer cells were performed using Neutral red assay. On the other hand, their apoptotic effect and their capacity to induce cell cycle arrest were investigated by flow cytometry assay. The effect of Seagrasses on the mitochondrial membrane potential (ΔψM) was studied by using JC-1 mitochondrial membrane potential assay kit in Seagrasses treated cancer cells to Δψ Caspases 3/7activity was examined using the colorimetric method. Gene expression analysis and quantitative real time RT-PCR for the sea grasses on MCF-7 was performed. Immune-blotting technique for Bcl-2 and p53 was investigated.ResultsHPLC analysis demonstrated that the extracts contained mainly flavonoids and polyphenols such as Caffeic acid, Chlorogenic acids, catechin and kaempferol that might be responsible for these anticancer effects. Seagrasses alcoholic crude extract markedly suppressed the growth and expansion of MCF-7 cells concentration-dependently with no toxicity against normal human skin fibroblast HSF. Thalassia hemprichii and Enhalus acoroides trigger mode of cell death primarily via apoptosis as confirmed by the flow cytometry. Additionally, they have ability to induce G0/S cell cycle arrest in MCF-7. The data showed the depletion in mitochondrial membrane potential (ΔψM) in the treated cells dose-dependently Caspases 3/7activities markedly increased following 24 h treatment. Finally, Gene expression analysis showed a marked reduction in Bcl-2, Survivin and CDC2 gene expression levels and a significant increase in the expression of p53 and CC2D1A as compared to control cells.ConclusionIn summary, the Methanolic extract of seagrass, Thalassia hemperchii and Enhalus ocoroides are able to induce concentration-dependent cytotoxic effects in human MCF-7 cells through intrinsic pathway of apoptosis in MCF-7 cells. This study reveals the beneficial importance of sea grasses as a source of anticancer agents. Further in vivo study is recommended for the active isolated biomolecules.

Combined SERS-Raman screening of HER2-overexpressing or silenced breast cancer cell lines

BackgroundBreast cancer (BC) is a heterogeneous neoplasm characterized by several subtypes. One of the most aggressive with high metastasis rates presents overexpression of the human epidermal growth factor receptor 2 (HER2). A quantitative evaluation of HER2 levels is essential for a correct diagnosis, selection of the most appropriate therapeutic strategy and monitoring the response to therapy.ResultsIn this paper, we propose the synergistic use of SERS and Raman technologies for the identification of HER2 expressing cells and its accurate assessment. To this end, we selected SKBR3 and MDA-MB-468 breast cancer cell lines, which have the highest and lowest HER2 expression, respectively, and MCF10A, a non-tumorigenic cell line from normal breast epithelium for comparison. The combined approach provides a quantitative estimate of HER2 expression and visualization of its distribution on the membrane at single cell level, clearly identifying cancer cells. Moreover, it provides a more comprehensive picture of the investigated cells disclosing a metabolic signature represented by an elevated content of proteins and aromatic amino acids. We further support these data by silencing the HER2 gene in SKBR3 cells, using the RNA interference technology, generating stable clones further analysed with the same combined methodology. Significant changes in HER2 expression are detected at single cell level before and after HER2 silencing and the HER2 status correlates with variations of fatty acids and downstream signalling molecule contents in the context of the general metabolic rewiring occurring in cancer cells. Specifically, HER2 silencing does reduce the growth ability but not the lipid metabolism that, instead, increases, suggesting that higher fatty acids biosynthesis and metabolism can occur independently of the proliferating potential tied to HER2 overexpression.ConclusionsOur results clearly demonstrate the efficacy of the combined SERS and Raman approach to definitely pose a correct diagnosis, further supported by the data obtained by the HER2 gene silencing. Furthermore, they pave the way to a new approach to monitor the efficacy of pharmacologic treatments with the aim to tailor personalized therapies and optimize patients’ outcome.

Measurement properties of the Iranian version of the breast cancer perception scale (BCPS) according to the COSMIN checklist

BackgroundBreast cancer is a prevalent cancer characterized by its aggressive nature and potential to cause mortality among women. The rising mortality rates and women’s inadequate perception of the disease’s severity in developing countries highlight the importance of screening using conventional methods and reliable scales. Since the validity and reliability of the breast cancer perception scale (BCPS) have not been established in the Iranian context. Therefore, this study aimed to determine the measurement properties of the BCPS in women residing in Tabriz, Iran.MethodsThe present study comprised a cross-sectional design, encompassing a sample of 372 Iranian women. The participants were selected through a multi-stage cluster random sampling technique conducted over a period spanning from November 2022 to February 2023. The measurement properties of the Iranian version of BCPS were assessed following the guidelines outlined in the COSMIN checklist. This involved conducting various steps, including the translation process, reliability testing (internal consistency, test-retest reliability, and measurement error), and methodological tests for validity (content validity, face validity, construct validity, and hypothesis testing). The study also investigated the factors of responsiveness and interpretability. The presence of floor and ceiling effects was assessed.ResultsThe internal consistency of the scale was assessed using Cronbach’s alpha, yielding a satisfactory value of 0.68. Additionally, McDonald’s omega (95% CI) was computed, resulting in a value of 0.70 (0.66 to 0.74). Furthermore, the test-retest reliability was evaluated, revealing a high intraclass correlation coefficient (ICC) of 0.97 (95% CI: 0.94 to 0.99). The CVI, CVR, and impact scores of the BCPS were determined to be 0.98, 0.95, and 3.70, respectively, indicating favorable levels of content and face validity. To assess construct validity, an examination of the Exploratory Factor Analysis (EFA) was conducted on a set of 24 items. This analysis revealed the presence of six distinct factors, which collectively accounted for 52% of the cumulative variance. The fit indices of the validity model (CFI = 0.91, NFI = 0.96, RFI = 0.94, TLI = 0.90, χ2/df = 2.03, RMSEA = 0.055 and SRMR = 0.055) were confirmed during the confirmatory factor analysis (CFA). The overall score of BCPS exhibited a ceiling effect of 0.3%. The floor effect observed in the overall score (BCPS) was found to be 0.5%. Concerning the validation of the hypothesis, Spearman’s correlation coefficient of 0.55 was obtained between the BCPS and the QLICP-BR V2.0. This correlation value signifies a statistically significant association. Furthermore, it is worth noting that the minimum important change (MIC) of 3.92 exhibited a higher value compared to the smallest detectable change (SDC) of 3.70, thus suggesting a satisfactory level of response.ConclusionsThe obtained findings suggest that the Iranian version of the BCPS demonstrates satisfactory psychometric properties for assessing the perception of breast cancer among Iranian women. Furthermore, it exhibits favorable responsiveness to clinical variations. Consequently, it can serve as a screening instrument for healthcare professionals to comprehend breast cancer and as a reliable tool in research endeavors.

Uncertainty affects cancer-related fatigue among breast cancer women undergoing peripherally inserted central catheter chemotherapy: the chain mediating role of psychological resilience and self-care

BackgroundBreast cancer patients undergoing chemotherapy via peripherally inserted central catheter often experience serious behavioral and psychological challenges, with uncertainty and cancer-related fatigue being prevalent issues that profoundly impact prognosis. Therefore, this study aimed to investigate the relationship between uncertainty and cancer-related fatigue by employing a chain mediation model to examine the potential mediating roles of psychological resilience and self-care.MethodsA cross-sectional study was conducted with 223 breast cancer patients receiving peripherally inserted central catheter chemotherapy at two tertiary affiliated hospitals of China Medical University in Liaoning, China, from February 2021 to December 2022. Participants completed self-reported questionnaires to assess uncertainty, psychological resilience, self-care, and cancer-related fatigue. The collected data were subsequently analyzed using Pearson’s correlation analysis, hierarchical regression analysis, and mediation analysis.ResultsUncertainty exhibited a significant positive correlation with cancer-related fatigue (p < 0.01) and a negative correlation with psychological resilience (p < 0.01) and self-care (p < 0.01). Uncertainty was found to impact cancer-related fatigue through three pathways: psychological resilience mediated the relationship between uncertainty and cancer-related fatigue (mediating effect = 0.240, 95% confidence interval: 0.188 to 0.298, effect ratio = 53.22%); self-care also mediated this relationship (mediating effect = 0.080, 95% confidence interval: 0.044 to 0.121, effect ratio = 17.74%); furthermore, there was a significant joint mediating effect of psychological resilience and self-care on the association between uncertainty and cancer-related fatigue (mediating effect = 0.042, 95% confidence interval: 0.021 to 0.068, effect ratio o = 9.31%).ConclusionThe findings of this study revealed that uncertainty not only directly influenced cancer-related fatigue, but also operated through the mediating effect of psychological resilience, self-care, and sequential mediation of psychological resilience and self-care. Interventions tailored for breast cancer patients receiving peripherally inserted central catheter chemotherapy should target these factors to help alleviate uncertainty, enhance psychological resilience, and improve self-care practices, thereby ameliorating cancer-related fatigue.

Mitochondrial transfer from Adipose stem cells to breast cancer cells drives multi-drug resistance

BackgroundBreast cancer (BC) is a complex disease, showing heterogeneity in the genetic background, molecular subtype, and treatment algorithm. Historically, treatment strategies have been directed towards cancer cells, but these are not the unique components of the tumor bulk, where a key role is played by the tumor microenvironment (TME), whose better understanding could be crucial to obtain better outcomes.MethodsWe evaluated mitochondrial transfer (MT) by co-culturing Adipose stem cells with different Breast cancer cells (BCCs), through MitoTracker assay, Mitoception, confocal and immunofluorescence analyses. MT inhibitors were used to confirm the MT by Tunneling Nano Tubes (TNTs). MT effect on multi-drug resistance (MDR) was assessed using Doxorubicin assay and ABC transporter evaluation. In addition, ATP production was measured by Oxygen Consumption rates (OCR) and Immunoblot analysis.ResultsWe found that MT occurs via Tunneling Nano Tubes (TNTs) and can be blocked by actin polymerization inhibitors. Furthermore, in hybrid co-cultures between ASCs and patient-derived organoids we found a massive MT. Breast Cancer cells (BCCs) with ASCs derived mitochondria (ADM) showed a reduced HIF-1α expression in hypoxic conditions, with an increased ATP production driving ABC transporters-mediated multi-drug resistance (MDR), linked to oxidative phosphorylation metabolism rewiring.ConclusionsWe provide a proof-of-concept of the occurrence of Mitochondrial Transfer (MT) from Adipose Stem Cells (ASCs) to BC models. Blocking MT from ASCs to BCCs could be a new effective therapeutic strategy for BC treatment.

Impact of breast cancer on in-hospital mortality and health care utilization in female heart failure patients: a retrospective cohort study

Background Heart failure (HF) and breast cancer are major health concerns with overlapping risk factors. This study investigated the impact of breast cancer on in-hospital mortality, length of stay, and health care charges in patients with HF. Methods A retrospective cohort study was conducted using data from the National Inpatient Sample, focusing on female patients diagnosed with both breast cancer and HF. A control group of patients with HF without breast cancer was also analyzed. Main outcomes included in-hospital mortality, length of stay, and health care charges. Statistical analysis involved logistic and linear regression models. Results The study included 17,551 unweighted cases of breast cancer, corresponding to 87,755 weighted cases. Breast cancer, particularly metastatic, was associated with increased in-hospital mortality across various types of HF. Patients with breast cancer and HF had longer hospital stays, which was more pronounced in metastatic cases. However, the impact on hospital charges was not consistent across the different HF types. Racial disparities were evident, with Native Americans showing the highest mortality risk in acute HF. Conclusion Breast cancer significantly increases the in-hospital mortality risk and length of hospital stay in patients with HF. These findings highlight the need for integrated cardiovascular and oncological care, especially in the presence of metastatic breast cancer. The study underscores the importance of tailored management strategies for patients with HF with concurrent breast cancer and points toward the necessity for addressing racial disparities in health care.