Background: In high-risk breast cancer patients with skin infiltration the administration of a uniform dose to superficial tissues is fundamental in order to reduce local skin relapse. A personalized bolus may prevent the potential standard bolus’ inadequate dose distribution due to air gaps between the bolus and the skin. In this pilot study, we introduced in clinical practice the use of a personalized 3D printed bolus filled with ultrasound transmission gel. Methods: Seven patients undergoing radiotherapy after mastectomy were selected. 3D printed bolus dosimetric assessment was performed with MOSFET dosimeters on an anthropomorphic phantom and subsequently on three selected cases with increasing bolus shape irregularity. Acute/late toxicity and local control was assessed. Results: Overall, for the clinical cases the percentage median difference between measured and calculated doses was -2.7% (-7.0%÷4.9%). Median follow-up was 21 months. After two years, one patient showed G2 pain, one patient manifested G1 telangiectasia, one patient showed G1 hyperpigmentation, and two patients had no relevant toxicity. Conclusions: Personalized 3D-printed bolus filled with ultrasound gel may easily reproduce the standard bolus’ consistency providing an accurate coverage of the target area with tolerable acute/late toxicity grades. This is a pilot study and further investigations are needed.

The binding activity of various trastuzumab biosimilars versus the branded trastuzumab towards the glycosylated extracellular domain of the HER2 target in the presence of pertuzumab was in-vestigated. We employed size exclusion chromatography with tetra-detection methodology to simultaneously determine absolute molecular weight, concentration, molecular size, and intrinsic viscosity. All trastuzumab molecules in solution exhibit analogous behavior in their binary action towards HER2 regardless of the order of addition of trastuzumab/pertuzumab. This analogous behavior of all trastuzumab molecules, including biosimilars, highlights the robustness and con-sistency of their binding activity towards HER2. Furthermore, the addition of HER2 to a mixture of trastuzumab and pertuzumab leads to increased formation of high-order HER2 complexes, up to concentrations of one order of magnitude higher than in the case of sequential addition. The observed increase suggests a potential synergistic effect between these antibodies, which could enhance their therapeutic efficacy in HER2-positive cancers. These findings underscore the im-portance of understanding the complex interplay between therapeutic antibodies and their target antigens, providing valuable insights for the development of more effective treatment strategies.

Background: Galectins are innate immune system regulators, associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Materials and Methodology: Prisma Health Cancer Institute’s Biorepository provided seventy-one breast cancer patient samples, including all four stages as well as major molecular subtypes and histologies of breast cancer. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin levels of patients’ sera were analyzed using enzyme-linked immunosorbent assay (ELISA) to measure the concentrations of galectins-1, -3, and -9. Analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes including pooled t-test, Wilcoxon test, ANOVA, Tukey’s range test, and Steel Dwass Method (α=0.05). Results: Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-1 and -9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have KIT or PIK3CA mutation compared to primary breast cancer samples. Conclusion: The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.

Breast cancer is the most prevalent malignancy among women globally. Early diagnosis and treatment improvements are leading to a growing population of survivors. This has increased the risk of developing contralateral breast cancer (CBC), a distinct occurrence in the opposite breast of a previously diagnosed patient. The treatment options for breast cancer are often mas-tectomy or lumpectomy. Patients with lumpectomy frequently undergo a contralateral reduc-tion procedure to achieve more symmetry after the primary breast cancer surgery. The reduc-tion specimen is usually routinely examined by pathology to check for malignancies. The exci-sion in pieces and the absence of specific markers or ink make an examination of tumor size and margin status more challenging, impacting treatment decisions. A new protocol introduced in July 2022 seeks to improve diagnostic precision and treatment planning by excision in toto, marking, and inking excised reduction tissue to examine and treat potential CBC more effectively.

Almost one fifth of breast cancer cases express Human Epidermal Growth Factor-2 (HER2), and such expression is associated with highly proliferative tumor and poor prognosis. The introduction of anti-HER2 therapies has dramatically changed the natural course of this aggressive subtype of breast cancer. However, anti-HER2 therapy can be associated with substantial toxicities, mostly cardiac, and high cost. Over the past few years, there has been growing interest in de-escalation of anti-HER2 therapies to minimize adverse events and healthcare costs, while maintaining the efficacy of treatment. Data from clinical observations and single-arm studies have eluted to the minimal impact of anti-HER2 therapy in low-risk patients, like those with node-negative and small tumors. Though single-arm, the APT trial, in which patients with node-negative, small tumors received single-agent paclitaxel for 12 cycles plus trastuzumab for 1 year, was a practice-changing study. Several other recently published studies, like the PERSEPHONE trial, have shown more convincing data that 6 months of trastuzumab is not inferior to 12 months, in terms of disease-free survival (DFS), suggesting that de-escalating strategies with shorter treatment may be appropriate for some low-risk patients. Other de-escalating strategies involved adaptive, response-directed approach, and personalized therapy that depends on tumor genomic profiling.

Breast cancer poses a global health challenge, yet the influence of ethnicity on the tumor microenvironment (TME) remains understudied. In this investigation, we examined immune cell infiltration in 230 breast cancer samples, emphasizing diverse ethnic populations. Leveraging tissue microarrays (TMAs) and core samples, we applied multiplex immunofluorescence (mIF) to dissect immune cell subtypes across TME regions. Our analysis revealed distinct immune cell distribution patterns, particularly enriched in aggressive molecular subtypes triple-negative and HER2-positive tumors. We observed significant correlations between immune cell abundance and key clinicopathological parameters, including tumor size, lymph node involvement, and patient overall survival. Notably, immune cell location within different TME regions showed varying correlations with clinicopathologic parameters. Additionally, ethnicities exhibited diverse distributions of cells, with certain ethnicities showing higher abundance compared to others. In TMA samples, patients of Chinese and Caribbean origin displayed significantly lower numbers of B cells, TAMs, and FOXP3-positive cells. These findings highlight the intricate interplay between immune cells and breast cancer progression, with implications for personalized treatment strategies. Moving forward, integrating advanced imaging techniques, and exploring immune cell heterogeneity in diverse ethnic cohorts can uncover novel immune signatures and guide tailored immunotherapeutic interventions, ultimately improving breast cancer management.

Intrinsic subtype of triple-negative breast cancer (TNBC) is based on genomic evaluation. In this study, we report the survival and pathological complete response (pCR) rates of TNBC patients subtyped by IHC and treated with neoadjuvant chemotherapy (NACT). A retrospective cohort of 187 TNBC patients who received NACT between 2008 and 2017 was used, and IHC subtyping was performed on biopsy specimens before chemotherapy. The subtyping revealed predominant basal-like tumors (IHC-BL, 61%), followed by basal-like immune-suppressed (IHC-BLIS, 31%), mesenchymal tumors (12.5%), luminal androgen receptor tumors (IHC-LAR, 12%) and basal-like immune-activated (IHC-BLIA, 10.9%). The pathological complete response (pCR) rate varied among subtypes, with IHC-BLIA showing the highest (30.0%) and IHC-LAR showing the lowest (4.5%). IHC-BLIS led in recurrence sites. Overall and disease-free survival analyses did not show significant differences among subtypes. Although, IHC-BLIA demonstrated a trend toward better survival and IHC-mesenchymal worse. Patients who achieved pCR exhibited significantly better disease-free survival and overall survival than non-responders. This study underscores the potential of IHC-based subtyping in TNBC management, highlighting distinct response patterns to neoadjuvant chemotherapy and potential implications for treatment strategies. Further research is warranted to validate these findings and explore tailored therapeutic approaches for specific TNBC subtypes.

In this study, we described the most critical risk factors for different malignancies including: breast, prostate, lung, and colorectal carcinoma among others, with an emphasis on modifiable risk factors. We revised the literature review about risk factors involved in the genesis of cancer in various databases, including articles indexed in PUBMED, SCOPUS, PMC, and Google Scholar. Awareness of risk factors enables conscious decisions to be made in an effort to combat malignancies. Knowing risk factors is a mode of fighting malignancy. Diet, lifestyle, practises, and laboratory/clinical interventions were among risk factors of diverse malignancy. Diet, lifestyle, laboratory/clinical interventions all contribute to the genesis and prognosis in a variety of malignancies. We concluded that abstaining from risk factors can prevent the development of many malignancies in a century where this conundrum is raising disproportionately. By informing the public about modifiable risk factors cancer mortality rates can be reduced. It is treated here is to make the public aware of the modifiable risks of cancers.

The role of postmastectomy radiotherapy and regional nodal irradiation after radical mastectomy is defined in high-risk patients with locally advanced tumors, positive margins, and unfavorable biology. The benefit of postmastectomy radiotherapy in intermediate-risk patients (T3N0 tumors) remains a matter of controversy. It has been demonstrated that radiotherapy after breast-conserving surgery lowers the locoregional recurrence rate compared with surgery alone and improves the overall survival rate. In patients with 4 or more positive lymph nodes or extracapsular extension regional lymph node irradiation is indicated regardless of the surgery type (breast-conserving surgery or mastectomy). Despite the consensus that patients with more than 3 positive lymph nodes should be treated with radiotherapy, there is a controversy regarding the recommendations for patients with one to three involved lymph nodes. In patients with N0 disease with negative findings on axillary surgery, there is a trend to administer regional lymph node irradiation in patients with a high risk of recurrence. In patients treated with neoadjuvant systemic therapy and mastectomy, adjuvant radiotherapy should be administered in case of clinical stage III and/or ≥ypN1. In patients treated with neoadjuvant systemic therapy and breast-conserving surgery, postoperative radiotherapy is indicated irrespective of pathological response.

Epidemiological studies on micronutrient consumption have reported protective associations in the incidence and/or progression of various cancer types. Supplementation with some of these micronutrients has been analyzed, showing chemoprotection, low toxicity, antiproliferation, and the ability to modify epigenetic signatures in various cancer models. The following review inves-tigates the reported effects of micronutrient intake or supplementation in breast cancer progres-sion. A PubMed search was conducted with the keywords “micronutrients breast cancer progres-sion,” and the results were analyzed. The selected micronutrients were: Vitamins (A, C, D, and E), Folic Acid, metals (Cu, Fe, Se, and Zn), fatty acids, polyphenols, and iodine. The majority of in vitro models showed antiproliferative, cell cycle arrest, and antimetastatic effects for almost all the micronutrients analyzed, but these effects do not reflect animal or human studies. Only one clinical trial with Vitamin D and one pilot study with molecular iodine showed favorable overall survival and disease-free interval.

Background: Although several studies have been conducted on the use of Artificial Intelligence (AI) in mammography (MG), research focusing on the diagnosis of metachronous bilateral breast cancer (BC), which is typically more challenging to diagnose, remains limited. This study assessed whether AI could enhance the detection of BC, achieving earlier or more accurate diagnoses than radiologists in cases of metachronous contralateral BC. Methods: The study included patients who underwent unilateral BC surgery and subsequently developed contralateral BC during follow-up. We evaluated the capability of the AI-supported MG diagnostic system FxMammo™ (FathomX Pte Ltd, Singapore) to diagnose BC more accurately or earlier than radiologists' assessments. This evaluation was supplemented by reviewing MG readings by radiologists. Results: Out of 1,101 patients who underwent surgery, 10 patients who had initially received a partial mastectomy and later developed contralateral BC were analyzed. The AI system identified malignancies in 6 cases (60%), while radiologists identified 5 cases (50%). Notably, two cases (20%) were diagnosed solely by the AI system. Additionally, for these cases, the AI system had identified malignancies a year prior to the conventional diagnosis. Conclusions: This study highlights the AI system's effectiveness in diagnosing metachronous contralateral BC via MG. In some cases, the AI system consistently diagnosed cancer at earlier than radiological assessments.

Breast Cancer metastasis remains a formidable challenge in cancer research, contributing significantly to patient mortality despite advances in medical research. Lung metastasis, associated with breast cancer, poses an ongoing clinical dilemma with limited curative treatment options. This study delves into the intricate mechanisms underlying Breast Cancer-Lung Metastasis (BC-LM) primarily focusing on the function of SH3PXD2B in maturation of invadopodia, inducing epithelial-to-mesenchymal transition, disruption of proteostasis network, and ultimately leading to metastasis of Breast Cancer (BC) cells. With an extensive analysis of differential gene expression using RNASeq data, comparing normal breast cancer cells to metastatic sub-populations in lung. Employing the New Tuxedo pipeline our investigation notably observes SH3PXD2B as a key regulator in lung metastasis samples. This trend is further substantiated by data from the Cancer Cell Line Encyclopedia (CCLE), and Human Protein Atlas (HPA) which highlights elevated SH3PXD2B expression in MDA-MB-468 cells, underscoring its significance in metastatic adenocarcinoma. Additionally, we checked the overall survival (OS) of metastatic breast cancer (MBC) patients pinpointing SH3PXD2B and its associated partners like SH3PXD2A, MMPs, CTTN, ADAMs, and EMT markers with substantial expression in both BC and lung cancer, prognosticating poorer patient survival. Further, our transcription factor – target gene (TFTG) network essentially elucidated the role of SH3PXD2B as a key node in the network unveiling its roles in regulating cell migration, communication, and developmental processes. Proteomics and Western blotting assays consistently confirm heightened SH3PXD2B expression in BC cell lines, reaffirming our findings. By employing computational structure biology along with cancer systems biology approach, we generated a high-confidence structural model of SH3PXD2B, indicating its SH3_2 and SH3_3 domains crucial for interactions with the drug molecules. Molecular docking simulations identify Eribulin as a promising therapeutic agent capable of targeting these domains. Thus, our multidisciplinary approach seamlessly amalgamates systems medicine principles, aiming to repurpose existing drugs that target SH3PXD2B based on molecular signatures. Targeted therapies have emerged as a promising avenue for addressing MBC and this mechanistic model introduces novel therapeutic avenues for the treatment of BC-LM patients.

The purpose of this study was to determine the change in overall survival (OS) for patients with de novo metastatic breast cancer (dnMBC) over time. We conducted a retrospective cohort study with 1981 patients with dnMBC diagnosed between January 1995 and December 2017 at The University of Texas MD Anderson Cancer Center. OS was measured from the date of diagnosis of dnMBC. OS was compared between patients diagnosed during different time periods: 5-year periods and periods defined according to when key agents were approved for clinical use. The median OS was 3.4 years. The 5- and 10-year OS rates improved over time across both types of time periods. A subgroup analysis showed that OS improved significantly over time for the estrogen-receptor-positive/HER2-positive (ER+/HER2+) subtype, and exhibited a tendency toward improvement over time for the ER-negative (ER-)/HER2+ subtype. Median OS was significantly longer in patients with non-inflammatory breast cancer (P = .02) and in patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all P <.0001). These findings showed that OS at 5 and 10 years after diagnosis in patients with dnMBC improved over time. The significant improvements in OS over time for the ER+/HER2+ subtype and the tendency toward improvement for ER-/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.

Background: Metformin is a drug used to treat patients with type 2 diabetes, especially those who suffer from obesity. It is also used in the treatment of women with polycystic ovary syndrome (PCOS). This disease has been shown to be related to insulin resistance and multiplied blood sugar ranges. Further, it has been found that the use of metformin improves the menstrual cycles and ovulation rates of these women. Methods: A structured questionnaire will be conducted to determine the prevalence of breast cancer among women using metformin in the Ha’il region. Result: Incidence of breast cancer among women using metformin in the Ha’il region is very low. Conclusions: According to previous findings, metformin has been linked to lower breast cancer risk in women with type 2 diabetes. Furthermore, the findings of this study have corroborated the literature for the same by indicating that there is a substantial connection between metformin use and a lower risk of breast cancer in women with type 2 diabetes

Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of tri-ple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs, so that the distinct pH of tumor cells, would stimulate the release of the drug and/or genetic materi-al. The current revision summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer.

Metastasis is a major cause factor for breast cancer (BC)-associated mortality. During the metastatic process, disseminated tumor cells (DTCs) detach from the primary sites, and enter the bloodstream and establish the secondary colonies. Recent studies have provided substantial evidence for the importance of Notch signaling in BC metastasis. Therefore, this review focuses on the mechanisms by which Notch contributes to the origin of BC DTCs, increases their motility, regulates their intravasation and extravasation, protects them from host surveillance, and finally facilitates colonization. Identification of the mechanisms underlying Notch-related BC metastasis will lead to the development of novel Notch-targeted therapeutic strategies to reduce metastasis and significantly improve outcomes.

Siam weed, scientifically known as Chromolaena odorata and belonging to the Asteraceae family, is a fast-growing plant with prolific seed production. Although it is a traditional medicinal plant, it has become an agricultural weed in Africa and Asia, posing a threat to biodiversity and causing environmental damage. Despite this, C. odorata is highly regarded as a medicinal herb in tropical Africa, with anticancer effects on breast, liver, and colorectal cancer. However, it is important to regulate the intake of the plant extract as it can have a hepatotoxic effect on liver cells at higher doses. Further research needs to be conducted on the plant extract, and proper orientation and knowledge of its oral daily administration are necessary. This review summarizes current scientific investigations using ethanolic and methanolic aqueous extracts of C. odorata leaves on various cancer cells, to uncover its potential as an anticancer agent. The investigations were sourced from online databases like Google Scholar, PubMed, and other online-based journals.

To systematically investigate the epidemiology of breast cancer risk factors in Iran, we performed a systematic search via PubMed, Scopus, Web of Science and Persian databases for identifying studies published on breast cancer risk factors up to March 2019. Meta-analyses were done for risk factors reported in more than one study. We calculated odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using a fixed/random-effects models.Thirty-nine studies entered into the meta-analysis. Pooling of ORs showed a significant harmful effect for risk factors including family history (OR: 1.80, 95%CI 1.47-2.12), HRT (OR: 5.48, 95%CI 0.84-1.74), ER positive (OR: 1.87, 95%CI 1.41-2.33), PR positive (OR: 1.84, 95%CI 1.38-2.29), stress condition (OR: 2.67, 95%CI 1.84-3.50), passive smokers (OR: 1.68, 95%CI 1.34-2.03), full-term pregnancy at age 30 (OR: 3.41, 95%CI 1.19-5.63), abortion (OR: 1.84, 95%CI 1.35-2.33), sweets consumption (OR: 1.71, 95%CI 1.32-2.11) and genotype Arg/Arg (crude OR: 1.59, 95%CI 1.07-2.10), whereas a significant protective effect for late menarche (OR: 0.58, 95%CI 0.32-0.83), nulliparity (OR: 0.68, 95%CI 0.39-0.96), 13 to 24 months of breastfeeding (OR: 0.68, 95%CI 0.46-0.90), daily exercise (OR: 0.59, 95%CI 0.44-0.73) and vegetable consumption (crude OR: 0.28, 95%CI 0.10-0.46).This study suggest that factors such as family history, HRT, ER and PR positive status, stress condition, passive smokers, late full-term pregnancy, abortion, sweets consumption and genotype Arg/Arg might increase risk of breast cancer development, whereas late menarche, nulliparity, 13-24 months breastfeeding, daily exercise and vegetable consumption had an inverse association with breast cancer development.

Regardless of the advances in our ability to detect early and treat breast cancer, it is still one of the common types of malignancy worldwide, with the majority of patients decease upon metastatic disease. Nevertheless, due to these advances, we have extensively characterized the drivers and molecular profiling of breast cancer and further dividing it into subtypes. These subgroups are based on immunohistological markers (Estrogen Receptor-ER, Progesterone Receptor-PR and Human Epidermal Growth Factor Receptor 2-HER-2) and transcriptomic signatures, with distinct therapeutic approaches and regiments. These therapeutic approaches include targeted therapy (HER-2+), endocrine therapy (HR+) or chemotherapy (TNBC) with optional combination radiotherapy, depending on clinical stage. Technological and scientific advances in the identification of molecular pathways that contribute to therapy-resistance and establishment of metastatic disease, have provided the rationale for revolutionary targeted approaches against Cyclin-Dependent Kinases 4/6 (CDK4/6), PI3 Kinase (PI3K), Poly ADP Ribose Polymerase (PARP) and Programmed Death-Ligand 1 (PD-L1), among others. In this review, we focus on the comprehensive overview of epidemiology and current standard of care treatment of metastatic breast cancer, along with ongoing clinical trials. Towards this goal, we utilized available literature from PubMed and ongoing clinical trial information from clinicaltrials.gov to reflect the up to date and future treatment options for metastatic breast cancer.

Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3-5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in triple-negative MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMEC) at 2.5% w/v, and it was found that MH reduced proliferation of MCF-7 cells but not that of HMEC. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, effects of MH induced activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions.

Breast cancer, when advancing to a metastatic stage, involves the liver, impacting over 50% of cases and significantly diminishing survival rates. Presently, a lack of tailored therapeutic protocols for Breast Cancer Liver Metastasis (BCLM) underscores the need for a deeper understanding of molecular patterns governing this complication. Therefore, by analyzing differentially expressed genes (DEGs) between primary breast tumors and BCLM lesions, it aimed to shed light on the diversities of this process. This research investigates Breast cancer liver metastasis relapse by employing a comprehensive approach that integrates data filtering, Gene Ontology and KEGG Pathway Analysis, Overall Survival analysis, identification of the Alteration in the DEGs, Visualization of Protein-Protein Interaction Network, Signor 2.0, identification of positively correlated genes, screening results of the function of hub genes, immune cell infiltration analysis, genetic alternation analysis, Copy number variant analysis, Gene to mRNA interaction, transcription factor analysis , autodocking and identification of Potential Treatment Target. This study’s integrative approach unveils metabolic reprogramming, suggesting altered PCK1 and LPL expression as key in breast cancer metastasis recurrence.

The aim of this study was to investigate the possible role of 99mTc-sestamibi in the regulation of cancer cell proliferation and apoptosis. To this end, Te in vivo values of 99mTc-sestamibi uptake have been associated to the in-situ expression of both Ki67 and caspase-3. For in vitro investiga-tions BT-474 cells were incubated with three different concentration of 99mTc-sestamibi: 10µg/ml –1µg/ml – 0,1µg/ml. Expression of caspase-3 and Ki67, as well as the ultrastructure of cancer cells, were evaluated at T0 and after 24, 48, 72 and 120 hours after 99mTc-sestamibi incubation. Ex vivo data strengthened the known association between the sestamibi uptake and the Ki67 expression. Linear regression analysis showed a significant association between the sestamibi uptake and the number of apoptotic cells evaluated as caspase-3 positive breast cancer cells. As concern the in vitro data, a significant decrease of the proliferation index was observed in breast cancer cells incubated with high concentration of 99mTc-sestamibi (10µg/ml). Amazingly, a significant increase in caspase-3 positive cells in cultures incubated with 10µg/ml 99mTc-sestamibi was observed. This study suggested the possible role of sestamibi in the regulation of pathophysiological process involved in breast cancer.

(1) Importance of problem: Breast cancer accounted for 685.000 deaths globally in 2020, and half of all cases occur in women with no specific risk factor beside gender and age-group. During last 4 decades we see a reduction by 40% of age-standardized breast cancer [1], which in turn means that the number of mastectomies performed for younger women increased, raising the need for adequate breast reconstructive surgery. Advances in oncological treatment have made it possible to limit the extent of what represents radical surgery for breast cancer, yet in the past decade, we see a marked trend toward mastectomy in breast conserving surgery eligible patients [2]. Prophylactic mastectomy has also registered an upward trend [3,4]. This trend together with new indication for breast reconstruction like chest feminization in transgender patients [5] have increased the need for breast reconstruction surgery. (2) Purpose: The purpose of this study is to analyze the types of reconstructive procedures, their indications, their limitations, their functional results and the safety profiles when used during the integrated treatment plan of the oncologic patient; (3) Methods: We conducted an extensive literature review of the main reconstructive techniques, especially the autologous procedures, summarized the findings and presented a few cases from our own experience for exemplification of the usage of breast reconstruction in oncologic patients. (4) Conclusions: Breast reconstruction has become a necessary step in the treatment of most breast cancers and many reconstructive techniques are now routinely practiced. Microsurgical techniques are considered the "gold standard", but they are not accessible to all services, from a technical or financial point of view, so pediculated flaps remain the safe and reliable option, along with alloplastic procedures, to improve the quality of life of these patients.

The search for improved therapeutic approaches to breast cancer are still on going. Breast tumor kinase (BRK, also known as PTK6) is one of the targets, it is highly expressed in breast carcinomas while displaying low or no expression in the normal mammary gland, which hints at the oncogenic role of this enzyme in breast cancer. In these twenty years, an increasing number of studies have focused on understanding the cellular roles of BRK in breast cancers. This review outlines the advances made towards understanding the cellular and physiological role of BRK, the molecular and chemical inhibitors and its therapeutic significance in breast cancer.

Breast cancer has an important incidence in the worldwide female population. Although alterations in the mitochondrial genome probably play an important role in carcinogenesis, the actual evidence is ambiguous and inconclusive. The purpose of the present work was to explore mitochondrial sequences of clinical cases with breast cancer from different origins and determine the polymorphisms associated. The search for complete and partial mtDNA sequences obtained from breast cancer patients and controls was performed in NCBI Genbank database. We identified 124 mtDNA sequences associated to breast cancer cases of which 86 were complete and 38 partial sequences. Of these 86 complete sequences, 52 belong to patients with a confirmed diagnosis of breast cancer and 34 sequences were obtained from healthy mammary tissue of the same patients used as controls. From mtDNA analysis, two polymorphisms with significative statistical differences were found in D130 in sequences analyzed: m.310del (rs869289246) in 34.6% (27/78) breast cancer cases and 61.7% (21/34) of controls; and m.315dup (rs369786048) in 60.2% (47/78) of breast cancer cases and 38.2% (13/34) of controls. Also, the variant m.16519T>C (rs3937033) was found in 59% of control sequences and 52% of breast cancer sequences with a significant statistical difference. Polymorphic changes are evolutionarily related to haplogroup H of Indo-European and Euro Asiatic origins, however, were found in all non-European sequences with breast cancer.

Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.

Breast cancer develops from cells lining the milk ducts and slowly grows into a lump or a tumour. Breast cancer may be invasive or non-invasive. Invasive cancer spreads from the milk duct or lobule to other tissues in the breast, whereas, non-invasive ones lack the ability to invade other breast tissues. Non-invasive breast cancer is called in situ and may remain inactive for entire lifetime. Due to heterogeneity nature of breast, density as well as masses is variable in size and shape. A dataset of 18056 patients are collected from 20 Government Hospitals and 50 Private Hospitals in West Bengal before COVID-19 and after COVID-19. The classification of patients are made on three classes- Normal, Sign of Abnormality and Abnormality. The reports of MRIs of patients in January 2020 and February 2020 are collected from different hospitals. It is treated as dataset before COVID-19 . MRIS of patients in April 2020 and May 2020 are dataset during COVID-19. The entire datasets are accumulated for testing of any change in patients MRIS after the official announcement of new virus COVID-19 in March 2020. The aim of the paper is to make a comparison of any change in size and shape of masses of MRIs of patients before and after COVId-19. All collected MRIs reports are diagnosed by radiologists of hospitals.

Given that 3-Phosphoinositide-dependent kinase 1 (PDK1) plays a crucial role in malignant biological behaviors of a wide-range of cancers, we further review the influence of PDK1 in breast cancer (BC). First, we describe the power of PDK1 in cellular behaviors and extensively demonstrate the interacting networks of PDK1 via PI3K-dependent/ PI3K-independent pathway. Then we enlighten the roles of PDK1 in carcinogenesis, growth and survival, metastasis, and chemoresistance in BC cells. More important, we sort the current preclinical or clinical trials of PDK1 targeted therapy in BC and find that even though at present no selective PDK1 inhibitor is available for BC therapy, but the combination trials of PDK1 targeted therapy and other agents have demonstrated some benefit. Thus, there is increasing anticipations that PDK1 targeted therapy will have its space in future therapeutic concepts of BC, and we hope to feature PDK1 in BC to the clinic and bring the new promising to patients for targeted therapies.

The Myc gene, widely studied in numerous cancer types, serves as a pivotal regulator of crucial cellular processes implicated in tumorigenesis, such as cell growth, proliferation, invasion, metastasis, and therapy resistance. LncRNAs have been identified as relevant partners of Myc. LncRNAs modulate chromatin structure and function, transcription, splicing, stability, and translation of mRNAs, thereby emerging as pivotal regulators in cell differentiation, metabolism, signaling. An intricate crosstalk exists between Myc and lncRNAs in a wide range of cancers, wherein they can physically and functionally interact through direct and indirect mechanisms. Some lncRNAs can regulate Myc activity at post-transcriptional level, affecting its stability, translation, or interactions with other proteins, thus acting as oncogenes, while others act as tumor suppressors. On the other hand, Myc can target numerous lncRNA genes and modulate their expression, affecting the expression of downstream targets involved in tumorigenesis. Given the significant role of the Myc-lncRNA network in various cancer types, exploring therapeutic strategies targeting these crucial cellular regulators is of utmost importance. This review article focuses on breast cancer, analyzing those lncRNAs influencing Myc as well as the Myc-regulated lncRNAs.

Classification algorithms are very widely used algorithms for the study of various categories of data located in multiple databases that have real-world implementations. The main purpose of this research work is to identify the efficiency of classification algorithms in the study of breast cancer analysis. Mortality rate of women increases due to frequent cases of breast cancer. The conventional method of diagnosing breast cancer is time consuming and hence research works are being carried out in multiple dimensions to address this issue. In this research work, Google colab, an excellent environment for Python coders, is used as a tool to implement machine learning algorithms for predicting the type of cancer. The performance of machine learning algorithms is analyzed based on the accuracy obtained from various classification models such as logistic regression, K-Nearest Neighbor (KNN), Support Vector Machine (SVM), Naïve Bayes, Decision Tree and Random forest. Experiments show that these classifiers work well for the classification of breast cancers with accuracy>90% and the logistic regression stood top with an accuracy of 98.5%. Also implementation using Google colab made the task very easier without spending hours of installation of environment and supporting libraries which we used to do earlier.

Breast cancer (BC) is one of the most common types of cancer in women. Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), exhibits a highly aggressive phenotype with increased metastasis and resistance to conventional treatments. Nanocarrier technology is consistently employed to overcome limitations associated with traditional breast cancer therapy. The targeted drug delivery approach using nanocarriers enhances bioavailability, prolongs circulation, and facilitates effective drug accumulation at the tumor site through active or passive targeting. Currently, the FDA has approved a few nanocarrier systems, and numerous nano formulations are undergoing preclinical and clinical development for breast cancer targeting. Common nanocarrier types include polymeric micelles, microemulsions, magnetic microemulsions, liposomes, dendrimers, carbon nanotubes, and magnetic nanoparticles (NPs). This review extensively explores the targeting potential of nanocarriers in breast cancer. This study will provide a concise summary of current advances in treatment of breast cancer and diagnostics.

CCNs are specific type of matricellular proteins, which are essential signaling molecules, and play multiple roles in multicellular eukaryotes. This family of proteins consists of six separate members in mammals. The architecture of CCN proteins is multimodular and comprises four distinct motifs. CCN proteins achieve their specific physiological functions by binding to integrin receptors. The CCN family has been implicated in both cure and disease with impacts on biological interactions, such as cell adhesion, chemotaxis and migration, mitogenesis, cell survival, angiogenesis, differentiation, tumorigenesis, immune functions, chondrogenesis, and wound healing. Breast cancer is the most commonly diagnosed cancer worldwide and the leading cause of cancer mortality among women triggered by atypical expression of CCNs. A favorable or unfavorable association between various CCNs has been reported in patients with breast carcinomas. Aberrant expression of CCN1 intensifies the proliferation of epithelial cells that line the lobes and ducts of the breast. Evidence also shows that the expression of CCN2 can ameliorate tumor growth and metastasis. However, CCN3 (NOV), CCN5 (WISP-2), and CCN6 (WISP-3) are consistent with neoplastic development and metastasis repression. Particular CCN members can develop tumors and cancer progression, whereas others can competitively counter the processes. Several studies have been conducted on CCN proteins and cancer in recent years. In our study, we intend to provide an overview of those research works while keeping breast carcinoma on focus. We believe that the importance of the CCN protein family in breast cancer should be reconsidered.

(1) Background: Retroareolar breast tumors are common, but they rarely progress to malignancy. This report presents a case of a 41-years-old woman with a superficial breast tumor, emphasizing the significance of considering a wide range of options when evaluating breast lumps. (2) Methods: The patient presented with a steadily growing, ulcerating superficial tumor in her left breast. To determine the nature of the tumor, a diagnostic assessment was conducted, which included a positron emission tomography (PET) scan and histological analysis. (3) Results: The diagnostic assessment confirmed the presence of a malignant Grade II superficial infiltrating ductal carcinoma. Following the diagnosis, the patient underwent a modified radical mastectomy under general anesthesia. Subsequently, she received four cycles of adjuvant chemotherapy, followed by taxol administrations. (5) Conclusions: This case report underscores the importance of conducting a thorough examination and maintaining a high index of suspicion for breast tumors. By documenting this case, the report contributes to the existing knowledge on various manifestations of breast cancer and highlights the necessity of early identification and aggressive treatment. This knowledge can be applied to identify and manage similar cases in the future, leading to improved patient outcomes.

(1) Background: Multi-year research into the synergistic effect of cyclophosphamide and complex composite double-stranded DNA preparation (DNAmix) has made it possible to develop the novel Karanahan technology for treating malignant tumors, which is based on the eradication of cancer stem cells; (2) Methods: Pilot clinical trials for Karanahan technology were conducted in 12 patients with advanced stage IV breast cancer; (3) Results: The findings indicate that the analyzed treatment regimen ensures a local positive therapeutic response, significantly increases patient survival time, and activates the adaptive antitumor immune response. Adjustment of the basic regimen of Karanahan technology has been developed, which consists of increasing the dose of the DNAmix complex composite double stranded DNA preparation and its lymphotropic administration to the main lymph depots simultaneously with intratumoral injection; (4) Conclusions: Karanahan technology has a promising therapeutic potential in the treatment of inoperable stage IV breast cancer.

PgRMC1 (progesterone receptor membrane component 1) is a progesterone-binding protein highly expressed in various cancer cells. Its expression has been associated with cancer development, chemoresistance, and poor prognosis in breast cancer through the regulation of drug and sterol metabolism, cell cycle, and apoptosis. However, the precise functions of PgRMC1 remain unclear. We examined PgRMC1 expression in breast cancer tissues and analyzed its correlation with clinicopathological characteristics and treatment response (n=112). PgRMC1 expression was detected in breast cancer tissue, while no immunoreactivity for PgRMC1 was observed in normal breast tissue. Notably, PgRMC1 expression levels were high in the HER2 subtype. Among patients treated with neoadjuvant chemotherapy, those with a poor pathological response had significantly higher PgRMC1 expression than those with a good response. PgRMC1 overexpression in breast cancer cell lines reduced chemosensitivity. Real-time qPCR analyses revealed that PgRMC1 induced the expression of differentiation markers, including CDH1 and KRT19, indicating that PgRMC1 is involved in the suppression of epithelial-mesenchymal transition and mammary luminal epithelial differentiation. Our findings suggest that PgRMC1 may contribute to chemoresistance and serve as a putative biomarker for assessing neoadjuvant chemotherapy sensitivity.

(1) Background: Breast cancer is the leading malignancy worldwide and in Ghana it has a poor overall survival. However, approximately 50% of cases are early stage disease and with advances in breast cancer treatment and improvement in survival, quality of life (QOL) becomes as im-portant as treatment of the disease. (2) Methodology: This was a cross-sectional study of survivors who had breast conserving surgery (BCS), mastectomy only (M) and mastectomy with breast re-construction (BRS) from 2016 to 2020 at a tertiary hospital in Ghana, comparatively assessing their QOL using EORTC QLQ C-30 and EORTC QLQ BR-23. (3) Results: The study participants had an overall Global Health Status (GHS) median score of 83.3 [IQR: 66.7-91.7] with no significant differences between the surgery types. The BRS group had a statistically significant lower median scores for the Functional scale (82.8 and 51.0) and the highest scores for the Symptomatic scale (15.7 and 16.5). Body image was significantly lowest for the BRS group 83.3 [68.8-91.7] and highest 100 [91.7-100] for the BCS group (p < 0.001). (4) Conclusion: There is a need to develop support systems tailored at improving the QOL of breast cancer survivors taking into consideration the type of surgery performed.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature data concerning the immunogenicity of breast cancer have been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune re-sponse in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ sub-types where increased TIL levels have been linked to better response to neoadjuvant chemotherapy and with improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes . In detail, TNBC shows the highest percentages of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points and scoring systems have been utilized across published studies. In the present paper an extensive review on the current knowledge of immune landscape of BC is provided. In detail TILS and PD-L1 expression across different BC subtypes is discussed also providing a guide for their pathological assessment and reporting.

Abstract On the background of new research results in screening of breast cancer, together with the expectation of the participants in a screening for breast cancer, the conventional mammography requires supplementation by means of tomosynthesis or additive ultrasound. Alternatively, ultrasound now seems to be an independent method of early detection of breast cancer because of its superior sensitivity, especially in the case of aggressive mammary carcinoma types. The MRI remains at present still a preferred method in high-risk cases and as an additive examination in case of insufficient presentation of the glandular tissue by conventional methods. MRI is also preoperatively valuable for more accurately measuring the extent of multifocal carcinomas.

The mammalian STE 20-like protein kinase 4 (MST4) gene is highly expressed in several cancer types, but little is known on the role of MST4 in breast cancer and the function of MST4 during epithelial-mesenchymal transition (EMT) has not been fully elucidated. Here, we report that overexpression of MST4 in breast cancer results in enhanced cell growth, migration, and invasion, whereas inhibition of MST4 expression significantly attenuates these properties. Further study shows that MST4 promotes EMT by activating Akt and its downstream signaling molecules such as E-cadherin/N-cadherin, Snail, and Slug. MST4 also activates AKT and its downstream pro-survival pathway. Furthermore, by analyzing breast cancer patient tissue microarray and silicon datasets, we found that MST4 expression is much higher in breast tumor tissue compared to normal tissue, and significantly correlates with cancer stage, lymph node metastasis and a poor overall survival rate (p<0.05). Taken together, our findings demonstrate the oncogenic potential of MST4 in breast cancer, highlighting its role in cancer cell proliferation, migration/invasion, survival, and EMT, suggesting a possibility that MST4 may serve as a novel therapeutic target for breast cancer.

Background: Monoclonal antibodies against PD-1 or PD-L1 are established in clinical practice for the treatment of both early and advanced/metastatic triple-negative breast cancer. Beyond the established immune checkpoints (ICPs) (PD-1 and CTLA-4) additional ICPs such as lymphocyte activation gene-3 (LAG-3) are subject of current research. In the present retrospective gene ex-pression analysis, we evaluated the prognostic significance of LAG-3 in 461 patients with early breast cancer. In addition, we examined whether there was a correlation between the different ICPs and CD8 expression. Methods: Using microarray-based gene expression analysis, we examined the prognostic signif-icance for metastasis-free survival (MFS) of LAG-3 mRNA expression in the whole cohort of 461 breast cancer patients and among different molecular subtypes. Correlations were analyzed us-ing Spearman-Rho correlation coefficient. Results: In the whole cohort, LAG-3 expression had no significant impact on MFS (p = 0.712, Log Rank). In the subgroup analyses, there was a trend, that higher LAG-3 expression was associated with favorable outcome in the luminal B (p = 0.217), basal-like (p = 0.370) and HER2 (p = 0.089) subtypes, although significance was not reached. In contrast, in multivariate Cox regression analysis adjusted for age, tumor size, axillary nodal status, histological grade of differentiation and the proliferation marker Ki-67, LAG-3 showed a significant influence on MFS (HR 0.574; 95% CI 0.369–0.894; p = 0.014). High LAG-3 significantly correlated with CD8 ( = 0.571; p < 0.001). Conclusion: LAG-3 expression had an independent impact on MFS. In addition to PD-1 and PD-L1, further immune checkpoints such as LAG-3 could serve as therapeutic targets in breast cancer.

Tissue inhibitors of metalloproteinases (TIMPs) are essential players during tumor progression in various types of cancer, including breast cancer. TIMPs regulate the activity of matrix metallo-proteinases (MMPs) at different levels. However, a dual role for TIMPs in breast carcinogenesis, either promoting or inhibiting tumor progression, has been observed. By a comprehensive bioin-formatics analysis using different databases, we report that of the four TIMPs, only TIMP-1 is overexpressed in tumor breast tissue. However, TIMP-2, TIMP-3, and especially TIMP-4 present lower levels in breast tumor tissue than in normal tissue. Interestingly, high levels of TIMP-1 are associated with shorter survival in breast cancer patients. In contrast, low TIMP-2, TIMP-3, and TIMP-4 levels are associated with poor survival. Function enrichment analysis showed that TIMP-3 has the highest interactions with its target proteins and a higher number of processes re-lated to mammary carcinogenesis. We found differential expression of TIMP-1 concerning TIMP-3 and TIMP-4 in breast cancer and normal tissue. TIMP-4 has a significant relationship with cancer staging, including tumor size, lymph node spread, and metastasis. The correlation between immune cell infiltrates and TIMP expression is of great importance as they provide in-formation on breast cancer diagnosis, prognosis, progression, and response to treatment.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

BOLD-100, a ruthenium-based complex, sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (also known as IT-139, NKP1339 or KP1339), is a novel small molecule drug that demonstrated a manageable safety profile at the maximum tolerated dose and modest antitumor activity in a phase I clinical trial. BOLD-100 has been reported to inhibit the upregulation of the endoplasmic reticulum stress sensing protein GRP78. However, response to BOLD-100 varies in different cancer models and the precise mechanism of action in high-response versus low-response cancer cells remains unclear. In vitro studies have indicated that BOLD-100 induces cytostatic rather than cytotoxic effects as a monotherapy. To understand BOLD-100 mediated signaling mechanism in breast cancer cells, we used estrogen receptor positive (ER+) MCF7 breast cancer cells to obtain gene-metabolite integrated models. Particularly, BOLD-100 significantly reduced expression of genes involved in the DNA repair pathway. BOLD-100 also induced reactive oxygen species (ROS) and phosphorylation of histone H2AX, gH2AX (Ser139), suggesting disruption of proper DNA surveillance. In estrogen receptor negative (ER-) breast cancer cells, combination of BOLD-100 with a PARP inhibitor, olaparib, induced significant inhibition of cell growth and xenografts and increased gH2AX. Thus, BOLD-100 is a novel DNA repair pathway targeting agent and can be used with other chemotherapies in ER- breast cancer.

Breast cancer is the leading cause of cancer deaths worldwide in women. This aggressive tumour can be categorized into two main groups: in situ and infiltrative, with the latter being the most common malignant lesions. The current use of Magnetic Resonance Imaging (MRI) was shown to provide highest sensitivity in the detection and discrimination between benign vs. malignant lesions, when interpreted by expert radiologists. In this article, we present the prototype of a Computer-Aided Detection/Diagnosis (CAD) system that could provide valuable assistance to the radiologist for the discrimination between in situ and infiltrating tumours. The system consists of two main processing levels: 1) Localization of possibly tumoral regions of interest (ROIs) through an iterative procedure based on intensity values (ROI Hunter) followed by a deep-feature extraction and classification method for false-positive rejection; 2) Characterization of the selected ROIs and discrimination between in situ and invasive tumour, consisting of Radiomics feature extraction and classification through a machine-learning algorithm. The CAD system was developed and evaluated using a DCE-MRI image database, containing at least one confirmed mass per image, as diagnosed by an expert radiologist. When evaluating the accuracy of the ROI Hunter procedure with respect to the radiologist-drawn boundaries, sensitivity to mass detection was found to be 75%. The AUC of the ROC curve for discrimination between in situ and infiltrative tumors was 0.70.

Breast cancer is an important disease that threatens the lives of women. The majority of breast screening health education is printed promotional material, which is ineffective in enhancing women’s knowledge on breast screening in Taiwan, and showed low breast cancer screening rate in women. This provided the impetus for us to carry out this study to understand the major barrier of women on breast cancer and screening procedures. This study used quasi-experimental design and purposive sampling. The study participants were 45–69 year-old women. Data collection was carried out before and after intervention. The health belief model was used as a research framework to examine changes in the study participants after multimedia health education intervention for detecting which factors most affect women's breast cancer screening behavior. Then we could make the policy for enhancing women's breast cancer screening in the future. Our study showed that after multimedia health education intervention, the scores of perceived susceptibility, perceived seriousness, perceived benefits, perceived barriers, cues to action, and self-efficacy in the experimental group were all significantly higher than the control group. We believe that the effectiveness of multimedia health education is better than traditional health education methods, and can enhance women to receive breast cancer screening.

Breast cancer remains a major public health concern, and early detection can result in more treatment options, which are crucial for improving survival rates. Metabolomics offers the potential to develop blood-based screening and diagnostics tools that are less invasive and more cost-effective. However, the inherent complexity of metabolomic datasets makes identifying the most diagnostically relevant biomarkers a difficult task, with multiple studies demonstrating lim-ited agreement on the specific metabolites and pathways involved. This study aims to identify a set of biomarkers for early diagnosis of breast cancer using metabolomics data. Plasma samples from 185 breast cancer patients and 53 controls (CHTN) were analyzed. We utilized univariate Naïve Bayes, L2-regularized Support Vector Machines, and Principal Component Analysis (PCA), along with feature engineering techniques, to select the most informative features. Multiple ma-chine learning models, including Support Vector Machines, Multidimensional Scaling, Logistic Regression, and Ensemble Learning were utilized for classification. The best-performing feature set comprised 4 biomarkers and 2 demographic variables, achieving an accuracy of 98%, demon-strating the potential for a robust, cost-effective, non-invasive breast cancer screening and diagnostic tool.

Breast cancer is the most common cancer in women. Cardiovascular diseases are common complications after chemotherapy due to the effect of the drug on lipid levels. This study aimed to explore the changes in lipid profiles in patients with breast cancer under chemotherapy. Methods: In this prospective study, 50 patients with breast cancer participated. Three biochemical-lipid hematological tests were performed: total cholesterol (TC), triglycerides (TG), High-Density Lipoprotein (HDL-C), and Low-Density Lipoprotein (LDL-C) before initiation (pre-chemotherapy), at the start (1st follow-up), and at the completion (2nd follow-up) of the first cycle of chemotherapy. Statistical significance was set at p&lt;0.05. Analyses were conducted using SPSS Statistical Software (version 22.0). Results: Mean TC values increased significantly at 2nd follow-up. TG values decreased significantly from 1st to 2nd follow-up. HDL-C was significantly lower at 1st follow-up compared to pre-chemotherapy and 2nd follow-up reaching similar to the initial levels. LDL-C values were significantly higher at 2nd follow-up compared to pre-chemotherapy measurement. Significantly positive correlations of BMI with pre-chemotherapy LDL-C, 1st follow-up TC, 1st follow-up LDL-C, 2nd follow-up TC, and 2nd follow-up LDL-C were found. Conclusions: There is a statistically significant increase in the levels of TC and LDL-C in breast cancer patients during chemotherapy. This study was not registered.

Breast cancer is the most prevalent type of disease among women. It has become one of the foremost causes of death among women globally. Early detection plays a significant role in administering personalized treatment and improving patient outcomes. Mammography procedures are often used to detect early-stage cancer cells. This traditional method of mammography while valuable has limitations of potential for false positives and negatives, patient discomfort, and radiation exposure. Therefore, there is a probe for more accurate techniques required in detecting breast cancer, leading to exploring the potential of machine learning in the classification of diagnostic images due to its efficiency and accuracy. This study conducted a comparative analysis of pre-trained CNNs (ResNet50 and VGG16) and Vision Transformers (ViT-Base and SWIN Transformer) with the inclusion of ViT-Base trained from scratch model architectures to effectively classify breast cancer mammographic images into benign and malignant cases. The Swin transformer exhibits superior performance with 99.8% accuracy and a precision of 99.8%. These findings demonstrate the efficiency of deep learning to accurately classify breast cancer mammographic images for the diagnosis of breast cancer, leading to improvement in patient outcomes.

Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced or high-risk tumors. However, a good response to NCT is not usually expected in ER+ tumors. Good results with primary ET, mainly in elderly women, have encouraged studies in other stages of life, and nowadays neoadjuvant endocrine treatment (NET) has become a useful approach to many ER+ breast cancers. The aim of this review is to provide an update on the current state of art regarding the present and the future role of NET.

In this paper, a mathematical model of breast cancer governed by a system of ordinary differential equations in the presence of chemotherapy treatment and ketogenic diet is discussed. Several comprehensive mathematical analysis was carried out using varieties of analytical methods to study the stability of the breast cancer model. Also, sufficient conditions on parameter values to ensure cancer persistence in the absence of anti-cancer drugs ketogenic diet and cancer emission when anti-cancer drugs, immune-booster, ketogenic diet are included were established. Furthermore, optimal control theory is applied to find out the optimal drug adjustment as an input control of the system therapies to minimize the number of cancerous cells by considering different controlled combinations of administering the chemotherapy agent and ketogenic diet using the popular Pontryagin’s Maximum Principle. Numerical simulations were presented to validate our theoretical results.

G protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions as well as in the pathology of many diseases including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review deals with the Prostaglandin E receptor EP4, a member of the EP family of GPCR, as a promising newer therapeutic target for treating breast cancer. We show that aberrant over-expression of cyclooxygenase (COX)-2, an inflammation-associated enzyme, occurring in 40-50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG) E2 production in the tumor milieu. They include inactivation of host anti-tumor immune (NK and T) cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis (due to upregulation of VEGF-A), lymphangiogenesis (due to upregulation of VEGF-C/D) and a stimulation of stem-like cell (SLC) phenotype in cancer cells. All these events were primarily mediated by activation of the PGE receptor EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could mitigate all these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs - miR526b and miR655, one of which (miR655) appears to be a potential blood biomarker in breast cancer patients, for monitoring SLC-ablative therapies such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents such as PD-1 or PD-L1 inhibitors.

ABSTRACT Background It is important to be able to predict, for each individual patient, the likelihood of later metastatic occurrence, because the prediction can guide treatment plans tailored to a specific patient to prevent metastasis and to help avoid under- or over-treatment. Deep Neural Network (DNN) learning, commonly referred to as deep learning, has become popular due to its success in image detection and prediction, but questions such as whether deep learning outperforms other machine learning methods when using non-image clinical data remain unanswered. Grid search has been introduced to deep learning hyperparameter tunning for the purpose of improving its prediction performance, but the effect of grid search on other machine learning methods are under-studied. In this research, we take the empirical approach to study the performance of deep learning and other machine learning methods when using non-image clinical data to predict the occurrence of breast cancer metastasis (BCM) 5, 10, or 15-years after the initial treatment. We developed DNN models as well as models using 9 other machine learning methods including Naive Bayes (NB), Logistic Regression (LR), Support Vector Machine (SVM), LASSO, Decision Tree (DT), k-Nearest Neighbors (KNN), Random Forrest (RF), AdaBoost (ADB), and XGBoost (XGB). We used grid search to tune hyperparameters for all methods. We then compared the deep learning models to the models trained using the 9 other machine learning methods. Results Based on the mean test AUC results, DNN ranks 6th, 4th, and 3rd when predicting 5-year, 10-year, and 15-year BCM respectively, out of 10 machine learning methods. The top performing methods in predicting 5-year BCM are XGB(1^st), RF(2^nd), and KNN(3^rd). For predicting 10-year BCM the top performers are XGB (1^st), RF(2^nd), and NB(3^rd) . Finally, for 15-year BCM the top performers are SVM (1^st), LR and LASSO (tied for 2^nd), and DNN (3^rd). The ensemble methods RF and XGB outperform other methods when data are less balanced, while SVM, LR, LASSO, and DNN outperform other methods when data are more balanced. Our statistical testing results show that at a significance level of 0.05 DNN overall performs no worse than other machine learning methods when predicting 5-year, 10-year, and 15-year BCM. Conclusions Our results show that deep learning with grid search overall performs at least as well as other machine learning methods when using non-image clinical data. It is interesting to note that some of the other machine learning methods such as XGB, RF, and SVM are very strong competitors of DNN when incorporating grid search. It is also worth noting that the computation time required to do grid search with DNN is way more than that required to do grid search with the other 9 machine learning methods.

This study aimed to identify microRNAs associated with histological grade using comprehensive microRNA analysis data obtained by next-generation sequencing in early-stage invasive breast cancer. RNA-seq data from normal breast and breast cancer samples were compared to identify candidate microRNAs with different expressions using bioinformatics. A total of 108 microRNAs were significantly differentially expressed between normal breast and breast cancer tissues. Using clinicopathological information and microRNA sequencing data of 430 patients with breast cancer from The Cancer Genome Atlas (TCGA), the differences in candidate microRNAs between low- and high-grade cases were compared. Comparing the expression of the 108 microRNAs between low- and high-grade cases, 25 and 18 microRNAs were significantly upregulated and downregulated, respectively, in high-grade cases. Clustering analysis of the TCGA cohort using these 43 microRNAs identified two groups strongly predictive of histological grade. miR-3677 is a microRNA upregulated in high-grade breast cancer. The outcome analysis revealed that patients with high miR-3677 expression had a significantly worse prognosis than those with low miR-3677 expression. This study showed that microRNAs were associated with histological grade in early-stage invasive breast cancer. These findings contribute to the elucidation of a new mechanism of breast cancer growth regulated by specific microRNAs.

Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contibution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, etiopathogenesis and treatment of this multifactorial disease. For the first time the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most the fields and subfields of breast cancer pathology. This single and integrated approach allows to advance a unidirectional program to treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor, then every phase of the disease and finally every individual patient.

Objective: Breast cancer (BC) is the most common cause of death among females. There are many prognostic systems, the most recent of which are the molecular subtypes. Recently, it was included that thyroid disease is a favorable factor for the patients with BC and that the thyroid hormones have an effect on the disease. Thyroid stimulating hormone (TSH), however, is thought to be unrelated to the cancer aggressiveness. In the current study we aimed to examine the status of the postoperative TSH levels, as well as the impact of the thyroid disease on the cancer aggressiveness. Methods: A retrospective comparative analysis of invasive BC patients was performed between 2017 and 2019 year. 111 patients were selected. They were divided into group A (n=62) and group B (n=49), based on the presence or absence of thyroid disease, respectively. The data was processed with SPSS version 25. Results: There is a significant difference between group A and group B concerning the molecular subtypes, ki-67, and estrogen receptor. The current study supports the fact that TSH is responsible for the aggressiveness of the invasive BC and not the thyroid hormones themselves. Moreover, based on the correlation analyses calcium levels preoperatively are linked to cancer aggressiveness and could be used as future prognostic factors. Conclusion: Indeed, the thyroid disease appears to have more favorable prognosis based on the molecular subtype frequency but more emphasis in future studies should be given to the TSH and its relation to the overall survival of the patients.

Metformin, a widely used anti-diabetic drug, has garnered attention for its potential in cancer management, particularly in breast and colorectal cancer. It is established that metformin reduces mitochondrial respiration, but its specific molecular targets within mitochondria vary. Proposed mechanisms include inhibiting mitochondrial respiratory chain Complex I and/or Complex IV, and mitochondrial glycerophosphate dehydrogenase, among others. These actions lead to cellular energy deficits, redox state changes, and several molecular changes that reduce hyperglycemia in type 2 diabetic patients. Clinical evidence supports metformin’s role in cancer prevention in type 2 diabetes mellitus patients. Moreover, in these patients with breast and colorectal cancer, metformin consumption leads to an improvement of survival outcomes and prognosis. The synergistic effects of metformin with chemotherapy and immunotherapy highlights its potential as an adjunctive therapy for breast and colorectal cancer. However, nuanced findings underscore the need for further research and stratification by molecular subtype, particularly for breast cancer. This comprehensive review integrates metformin-related findings from epidemiological, clinical, and preclinical studies in breast and colorectal cancer. Here, we discuss current research addressed to define metformin's bioavailability and efficacy, exploring novel metformin-based compounds and drug delivery systems, including derivatives targeting mitochondria, combination therapies, and novel nanoformulations, showing enhanced anticancer effects.

For decades since the central dogma, cancer biology research has been focusing on the involvement of genes encoding proteins. It has been not until more recent times that a new molecular class has been discovered, named non-coding RNA (ncRNA), which has been shown to play crucial roles in shaping the activity of cells. An extraordinary number of studies into shown that ncRNAs represent an extensive and prevalent group of RNAs, including both oncogenic or tumor suppressive molecules. Henceforth, various clinical trials involving ncRNAs as extra ordinary biomarkers or therapies have started to emerge. In this review, we will focus on the prognostic and diagnostic role of ncRNAs for breast cancer.

Although mammography has been the gold standard for early detection of breast cancer, if a woman has dense breast tissue, a false negative diagnosis may occur. Breast ultrasound, whether hand-held or automated, is a useful adjunct to mammography but adds extra time and cost. The primary aim was to demonstrate that our second-generation Aceso system, which combines full-field digital mammography (FFDM) and automated breast ultrasound (ABUS) in a single platform, is able to produce improved quality images that provide clinically meaningful results. Aceso was first tested using two industry standards: a CDMAM phantom to assess the FFDM images; and the CIRS 054GS phantom to evaluate the ABUS images. In addition, 25 women participated in a clinical trial: 14 were healthy volunteers while 11 were patients referred by the breast clinic at Groote Schuur Hospital. The CDMAM phantom results showed the FFDM results were better than EUREF’s standard of “acceptable” and were approaching “achievable”. The ABUS results showed lateral and axial spatial resolution of 0.5 mm and adequate depth penetration of 80 mm. Our second-generation Aceso system, with its improved quality of clinical FFDM and ABUS images, has demonstrated its potential for early detection of breast cancer in a busy clinic.

Molecular iodine (I2) induces apoptotic, antiangiogenic, and antiproliferative effects in breast cancer cells. Little is known about its effects on the tumor immune microenvironment. We studied the effect of oral (5 mg/day) I2 supplementation alone (I2) or together with conventional chemotherapy (Cht+I2) on the im-mune component of breast cancer tumors from a previously published pilot study conducted in Mexico. RNA-seq, I2 and Cht+I2 samples showed significant increases in expression of Th1 and Th17 pathways. Tumor immune composition determined by deconvolution analysis revealed significant increases in M0 macrophages and B lymphocytes in both I2 groups. Real-time RT-PCR showed that I2 tumors overexpress T-BET (p = 0.019) and interferon-gamma (IFNγ; p = 0.020) and silence tumor growth factor-beta (TGFβ; p = 0.049); whereas in Cht+I2 tumors, GATA3 is silenced (p = 0.014). Preliminary methylation analysis shows that I2 activates IFNγ gene promoter (by increasing its unmethylated form) and silences TGFβ in Cht+I2. In conclusion, our data showed that I2 supplements induce the activation of the immune response and that when combined with Cht, the Th1 pathways are stimulated. The molecular mechanisms involved in these responses are being analyzed, but preliminary data suggest that methylation/demethylation mechanisms could also participate.

Introduction: Antitumor host immune response is an important factor, but its role is not fully established. The role of tumor infiltrating lymphocytes (TIL) in breast cancer as an immunological biomarker has been significantly explored over the past years. The number of patients treated with neoadjuvant chemotherapy (NAC) increased and identification of a biomarker to predict the probability of pCR (pathological complete response) is a high priority. Materials and methods: We evaluated 334 cases of BC treated with NAC followed by surgical resection from 2020-2022 in Ist Clinic of Oncological Surgery, Oncological Institute "Prof Dr I Chiricuta" Cluj Napoca. Of the above, 122 cases were available for histological evaluation both in pre-NAC biopsy and post-NAC resection tissue. Evaluation of biopsy fragments and resection parts using hematoxylin eosin (H&amp;E). The TIL evaluation took place according to the recommendations of the International TIL Working Group (ITILWG). Results: There was a strong association between elevated levels of pre-NAC TIL. At the same time, there is a statistically significant correlation between stromal TIL and tumor grade, the number of lymph node metastases, the molecular subtype, and the number of mitoses (p &lt;0.005). Intratumoral TIL showed a significant correlation with tumor size, distant metastasis, molecular subtype, number of mitosis, stage and lymph node metastasis (p&lt;0.005). We also demonstrated that high pre-NAC TILs represent a strong predictive marker for pCR. Conclusion: This study reveals the role of TIL as a predictive biomarker in breast cancer not only for the well-established TNBC (triple negative breast cancer) and HER2+ (Her2 overexpressed) subtypes but also in Luminal A and B molecular subtypes. In this scenario, the evaluation of TILs as novel predictive and therapy-predicting factors should become a routinely performed analysis that could guide clinicians into the choice of the most appropriate therapy.

This longitudinal study aimed to analyze the effects of a team rowing-based training program on physical fitness and anthropometric parameters in female breast cancer survivors (n=40; 56.78±6.38 years). Participants were divided into two groups: one rowed in fixed seat rowing (FSR) boats (n=20; 56.35±4.89 years) and the other in sliding seat rowing (SSR) boats (n=20; 57.20±7.7 years). Both groups engaged in two 75-minute sessions per week for 24 weeks. Significant improvements were observed in both groups in resting heart rate (FSR: -10.65 bpm; SSR: -8.45 bpm), heart rate at the beginning of the 6-minute walk test (6MWT) (FSR: -10.7 bpm; SSR: -11.25 bpm), and heart rate at the end of the test (FSR: -13.85 bpm; SSR: -20.35 bpm). Blood pressure improved significantly in both diastolic blood pressure (FSR: -12.35 mmHg; SSR: -19.25 mmHg) and systolic blood pressure (FSR: -13 mmHg; SSR: -16.95 mmHg). Additionally, both groups increased the distance covered in the 6MWT (FSR: +63.05 m; SSR: +93.65 m). These results suggest that a rowing training program is a viable and safe activity for female breast cancer survivors, improving cardiac function, blood pressure, and cardiorespiratory capacity, particularly in sliding seat boats.

Triple negative breast cancer (TNBC) has a negative expression of estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptors (HER2). The survival rate for TNBC is generally worse than other breast cancer subtypes. TNBC treatment has made significant advances, but certain limitations remain. Treatment for TNBC can be challenging since the disease has various subtypes. Individualized therapy is recommended rather than generalized therapy, given the genetic variations among these TNBC subtypes. A precise and effective treatment for TNBC requires identifying prognostic markers. Depending on the type and stage of TNBC, patients are treated with various therapeutic interventions. A variety of treatment options are available, such as chemotherapy, immunotherapy, radiotherapy, and surgery. Chemotherapy is the most common of these options. TNBC is generally treated with systemic chemotherapy using drugs such as anthracyclines and taxanes in the neoadjuvant or adjuvant settings. Developing resistance to anticancer drugs and off target toxicity are the primary hindrances to chemotherapeutic solutions for cancer. It is imperative that researchers, clinicians, and pharmaceutical companies work together to develop effective treatment options for TNBC. Several studies have suggested nanotechnology as a potential solution to the problem of suboptimal TNBC treatment.

The purpose of this longitudinal study was to determine the effects of a rowing training program on physical fitness and body composition in female breast cancer survivors (56.78 ± 6.38 years). Over six months, the participants (n=40) performed two training sessions per week for an average of 75 minutes, combining resistance and muscle strength exercises with rowing. To evaluate the impact of the program, physical fitness tests and anthropometric measurements were carried out before and after the training protocol. The results show statistically significant improvements in measures such as weight (-1.84 kg), BMI (-0.7 kg/m2), hip (-3.24 cm) and waist circumference (-2.45 cm). In addition, variables associated with physical fitness also improved including leg strength (3.04 cm), dominant handgrip strength (4.24 kgf), non-dominant handgrip strength (3.49 kgf), aerobic endurance (78.35 m) and muscle flexibility (3.96 cm). We can therefore conclude that a rowing-based exercise program is an effective strategy to improve physical fitness in this type of population, yielding improvements in both anthropometric measurements and basic physical capacity variables, essential factors for better health and quality of life.

(1) Background: Triple negative breast cancer (TNBC) is a distinct subgroup of breast cancer presenting high level of recurrence and neo-adjuvant chemotherapy is beneficial in its therapy management. Anti-PD-L1 immunotherapy improves effect of neo-adjuvant therapy in TNBC. (2) Methods: Immune-modulation and ferroptosis related R-packages were developed for integrative transcriptome to analyze transcriptome datasets: TNBC cells stimulated with ferroptosis inducers (GSE173905, GSE154425), breast tumors with clinical data (TCGA and METABRIC cohorts). Protein level validation was investigated through protein atlas proteome experiments. (3) Results: Erastin/RSL3 ferroptosis inducers up-regulate CD274 in TNBC cells (MDA-MB-231 and HCC38). In breast cancer, CD274 expression is associated to overall survival. Breast tumors presenting high expression of CD274 up-regulated some ferroptosis drivers associated to prognosis: IDO1, IFNG and TNFAIP3. CD274-ferroptosis-driver score computed on breast tumor transcriptome stratified patients on their prognosis: low score was observed in basal subgroup with higher level of recurrent risk scores: oncotypeDx, ggi and gene70 scores. In METABRIC cohort, CD274, IDO1, IFNG and TNFAIP3 were found overexpressed in TNBC subgroup. CD274-ferroptosis-driver score was found associated to overall survival independently of TNM classification and age diagnosis. Tumor expression of CD274, TNFAIP3, IFNG and IDO1 in biopsy of breast ductal carcinoma was confirmed at protein level (4) Conclusion: Ferroptosis inducers up-regulate PD-L1 in TNBC cells, known as effective target of immunotherapy in high risk early TNBC which received neo-adjuvant therapy. Basal and TNBC tumors highly expressed CD274 and ferroptosis drivers: IFNG, TNFAIP3 and IDO1. CD274-ferroptosis driver score is associated to prognosis and to the risk of recurrence in breast cancer. A potential synergy of ferroptosis inducers with anti-PD-L1 immunotherapy is suggested in recurrent TNBC.

Cancer stem cell (CSC) has paved the way to many fundamental and translational studies. Recent studies have highlighted differentiated breast cancer cells (non-CSCs) switching phenotype to CSCs in response to various stimuli, depicting the existence of cancer stem cell plasticity. Although strategies to reduce the phenotypic plasticity of non-CSCs into CSCs are likely to prevent treatment-resilient cancer cells driving recurrence, most phenotypic plasticity mechanisms involve Notch, Wnt or MAPK signaling pathways. In this study, breast cancer cells were irradiated to identify soluble reprogramming factors. Using conditioned medias, protein arrays analyses, flow cytometry and in cellulo/in vivo functional assays, we demonstrated, for the first time, that radiation-induced chemokine expression, especially CXCL1 and CCL5 and their receptors CXCR2, CCR1 and CCR5, stimulates reprogramming of breast non-CSCs into CSCs. Treatment of non-CSCs with recombinant CXCL1 and CCL5 is sufficient to induce cell reprogramming, while their inhibition can be used to prevent reprogramming and sensitize tumor to radiation. Moreover, analysis of gene expression profiles from 38 public merged databases demonstrated that combined over-expression of CXCL1/CXCR2, CCL5/CCR1 or CCL5/CCR5 has a poorer prognosis in patients treated with radiotherapy, suggesting a promising way for patient stratification, where individuals with elevated cytokine levels could benefit from radiotherapy in conjunction with cytokine inhibitors. Taken together, our findings provide a rationale to consider these axes as potential targets and predictive biomarkers in breast cancer patients.

Idiopathic granulomatous mastitis (IGM) is a rare condition characterised by chronic inflammation and granuloma formation in the breast. The aetiology of IGM is unclear. By focusing on the protein-coding regions of the genome, where most disease-related mutations often occur, whole-exome sequencing (WES) is a powerful approach for investigating rare and complex conditions, like IGM. We report WES results on paired blood and tissue samples from eight IGM patients. Samples were processed using standard genomic protocols. Somatic variants were called with two analytical pipelines: nf-core/sarek with Strelka2 and GATK4 with Mutect2. Our WES study of eight patients did not find evidence supporting a clear genetic component. The discrepancies between variant calling algorithms, along with the considerable genetic heterogeneity observed amongst the eight IGM cases, indicate that common genetic drivers are not readily identifiable. With only three genes, CHIT1, CEP170, and CTR9, recurrently altered in multiple cases, the genetic basis of IGM remains uncertain. The absence of validation for somatic variants by Sanger sequencing raises further questions about the role of genetic mutations in the disease. These observations suggest that IGM may be influenced by non-genetic factors, such as environmental triggers or immune system dysregulation, rather than being primarily a genetic disorder.

Language barriers exacerbate health disparities among minorities. This study highlights the efficacy of simple interventions in mitigating language barriers, optimizing clinic efficiency, and enhancing preparedness for surgical procedures in Spanish-speaking (SS) females diagnosed with breast cancer in a safety net community hospital. A bilingual questionnaire was given to English and SS patients during their initial clinic visit. Additionally, a bilingual handout on surgical options and postoperative care was provided to selected surgical patients. Among the 41 patients studied, those who completed the questionnaire had an average encounter time of 27.06 minutes, compared to 45.26 minutes for those who did not. For SS patients, the average encounter time with the questionnaire was 34.07 minutes versus 46.54 minutes without it. The average cost of a medical interpreter was $17.04 with the questionnaire, versus $23.27 without. All SS patients who received the educational handout expressed greater satisfaction and understanding of their treatment plans and were less likely to require additional pre-surgery visits. This study demonstrated how the simple implementation of a translated questionnaire can reduce interpretation cost, encounter time, and improve clinic flow. Furthermore, utilizing a bilingual surgical educational handout enhances patient understanding, surgery readiness and reduces unnecessary additional visits.

Male breast cancers are uncommon, as men account for less than 1 percent of all breast carcinomas. Among the predisposing risk factors for male breast cancer, the following appear to be significant: a) breast/chest radiation exposure, b) estrogen use, diseases associated with hyper-estrogenism, such as cirrhosis or Klinefelter syndrome, and c) family health history. Furthermore, there are clear familial tendencies, with a higher incidence among men who have a large number of female relatives with breast cancer and d) major inheritance susceptibility. Moreover, in families with BRCA mutations, there is an increased risk of male breast cancer, although the risk appears to be greater with inherited BRCA2 mutations than with inherited BRCA1 mutations. Due to diagnostic delays, male breast cancer is more likely to present at an advanced stage. A core biopsy or a fine needle aspiration must be performed to confirm suspicious findings. Infiltrating ductal cancer is the most prevalent form of male breast cancer, while invasive lobular carcinoma is extremely uncommon. Male breast cancer is almost always positive for hormone receptors. A worse prognosis is associated with a more advanced stage at diagnosis for men with breast cancer. And randomized controlled trials which recruit both female and male patients should be developed in order to gain more consistent data on the optimal clinical approach.

A brand-new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this Unitarian perspective based upon that the hydrogen ion (H+) dynamics of cancer, allows understanding and integrating the many dualisms, confusions, and paradoxes of the disease. The new H+-related wide range model can embrace under a unique frame of mind the many aspects of the disease and at the same time therapeutically interfere with most, if not with all, the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC here reviewed may be beneficial for all types and stages of the disease. In this vein, we have attempted a mega synthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide range approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of a pH-related drugs nowadays available for the treatment of breast cancer is advanced.

Cumulative evidence attests to the essential roles of commensal microbes in the physiology of the hosts. Although microbiome has been a major research subject since the time of Luis Pasteur and William Russell over 140 years ago, recent findings that certain intracellular bacteria contribute to the pathophysiology of healthy or diseased tissues have brought the field of microbiome to a new era of investigation. In particular, in the field of breast cancer research, breast-tumor resident bacteria are deemed to be the essential players of tumor initiation and progression. This is a resurrection of Russel’s bacterial cause of cancer theory abandoned over 100 years ago. This review will introduce some of the recent findings that exemplify the roles of breast tumor-resident microbes in breast carcinogenesis and metastasis and provide mechanistic explanations of these phenomena. Such information would be able to justify the utility of breast-tumor resident microbes as biomarkers for disease progression and therapeutic targets.

Background: As the most invasive breast cancer (BrCa), triple-negative BrCa (TNBC) has the worst survival. The use of dexmedetomidine potentially affected BrCa surgery and dexmedetomidine was reported to have direct effects on TNBC cells. The objective of this study is to explore the mechanisms underlying the effect of dexmedetomidine on TNBC. Methods: Dexmedetomidine targets were predicted using The Cancer Genome Atlas data SwissTargetPrediction. Cell lines MDA-MB-231, MCF7, and MCF10A were used to validate the targets in TNBC with both clinical samples and cell lines. Cancer cell lines and normal breast cell lines were grouped in cancer and normal groups respectively. Both groups were exposed to dexmedetomidine treatment. Cell Counting Kit-8 was used to determine the effect of dexmedetomidine on cells with target silencing. The binding model of the candidate targets was docked and critical amino acids were mutated to validate the binding model. Results: Dexmedetomidine selectively inhibits cancer cells. Catalytic subunit of the DNA-dependent protein kinase (PRKDC), indoleamine 2,3-dioxygenase 1 (IDO1), opioid receptor kappa 1 (OPRK1), glutaminyl-peptide cyclotransferase (QPCT), macrophage migration inhibitory factor (MIF), potassium voltage-gated channel, subfamily H (Eag-related), member 2 (KCNH2), cholinergic receptor, muscarinic 3 (CHRM3), and potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 (KCNN4) were identified as dexmedetomidine targets in TNBC. The expression levels of PRKDC, IDO1, MIF, KCNH2, CHRM3, and KCNN4 were found to be upregulated in TNBC tissues compared to non-TNBC tissues(p<0.05). Silencing of these genes was found to reduce the sensitivity of TNBC cells to dexmedetomidine(p<0.05). This effect was counteracted when the silenced genes were overexpressed, resulting in an increase in the sensitivity of cells to dexmedetomidine (p<0.05). Furthermore, a direct interaction between dexmedetomidine and IDO1 and CHRM3 was observed, which regulated the sensitivity of cells to dexmedetomidine(p<0.05).Conclusion: IDO1 and CHRM3 are direct targets of dexmedetomidine in TNBC.

Venoms are a rich source of bioactive compounds, and among them is leberagin-C (Leb-C), a disintegrin-like protein derived from the venom Macrovipera lebetina transmediterrannea snakes. Leb-C has shown promising inhibitory effects on platelet aggregation. Previous studies have demonstrated that this SECD protein specifically targets α5β1, αvβ3 and αvβ6 integrins through a mimic mechanism of RGD disintegrins. In our current study, we focused on exploring the potential effects of Leb-C on metastatic breast cancer. Our findings revealed that Leb-C disrupted the adhesion, migration, and invasion capabilities of MDA-MB-231 breast cancer cells and its highly metastatic D3H2LN sub-population. Additionally, we observed significant suppression of adhesion, migration, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs). Furthermore, Leb-C demonstrated a strong inhibitory effect on fibroblast growth factor 2-induced proliferation of HUVEC. We conducted in vivo experiments using nude mice and found that treatment with 2 µM of Leb-C resulted in a remarkable 73% reduction in D3H2LN xenograft tumor size. Additionally, quantification of intratumor microvessels revealed a 50 % reduction in tumor angiogenesis in xenograft after 21 days of twice-weekly treatment with 2 µM of Leb-C. Collectively, these findings suggest the potential utility of this dinsintegrin-like protein for inhibiting aggressive and resistant metastatic breast cancer.

MiRNAs are 20-22 nucleotide long single-stranded non-coding RNA sequences, which can regulate post transcriptional activity of mRNA by binding with it at 3’UTR region (untranslated region). Thus deregulation of miRNA expression is responsible for dysregulating mRNA function which contributes in developing various diseases as well as cancerous phenotypes. Alteration of single nucleotide in miRNA sequence is one of the reasons behind deregulation of miRNA expression. The most frequent carcinoma in current day is breast cancer which causes a high mortality among women around the world as well as India. Despite of the advancement of diagnostic tools, strategies and treatment, the cases of breast cancer is increasing every year. There are plenty of biomarkers like ER, PR, Her2, Ki-67, etc available which are frequently used in diagnosis and treatment of breast cancer. After the discovery of MiRNA in 1993 in Caenorhabiditis elegans, it is attracting all the limelight in diagnosis and treatment of different carcinomas as well as breast cancer. In this review we will discuss on involvement of different types of MiRNAs and miR SNPs in breast cancer occurrence and susceptibility in a detailed manner.

Breast cancer stands as the prevailing malignancy across all six Gulf Cooperation Council (GCC) nations. In this literature review, we highlighted the incidence and trend of BC in the GCC. Most of the studies reported a consistent increase in BC incidence over the past decades, which was particularly attributed to the adoption of a westernized lifestyle in the region and the implications of emerging risk factors and other environmental and societal factors, the increase in screening uptake, as well as the improvement in data collection and reporting in the GCC. The data about BC risk factors in GCC was limited. In this geographic region, breast cancer frequently manifests with distinctive characteristics, including an early onset, typically occurring before the age of 50, an advanced stage at presentation, and a higher pathological grade. Additionally, it often exhibits more aggressive features such as human epidermal growth factor receptor 2 (HER2) positivity or the presence of triple-negative (TN) attributes, particularly among younger patients. Despite the growing body of literature on breast cancer in the GCC, data pertaining to survival rates are, regrettably, meager. Reports on breast cancer survival rates emanating from the GCC region are largely confined to Saudi Arabia and the United Arab Emirates (UAE). In the UAE, predictive modeling reveals 2-year and 5-year survival rates of 97% and 89%, respectively, for the same period under scrutiny. These rates, when compared to Western counterparts such as Australia (89.5%) and Canada (88.2%), fall within the expected range. Conversely, Saudi Arabia reports a notably lower 5-year survival rate, standing at 72%. This disparity in survival rates underscores the need for further research directed towards elucidating risk factors and barriers that hinder early detection and screening. Additionally, there is a pressing need for expanded data reporting on survival outcomes within the GCC. In sum, a more comprehensive and nuanced understanding of breast cancer dynamics in this region is imperative to inform effective strategies for prevention, early detection, and improved patient outcomes.

Background: We previously found that QNBC tumors are more frequent in African Americans compared to TNBC tumors. To characterize this subtype further, we sought to determine the miRNA-mRNA profile in QNBC patients based on race. Methods: Both miRNA and mRNA expression data were analyzed from TCGA and validated using datasets from the METABRIC, TCGA proteomic, and survival analysis by KMPLOT. Results: miRNA-mRNAs which include FOXA1 and MYC (mir-17/20a targets); GATA3 and CCNG2 (mir-135b targets); CDKN2A, CDK6, and B7-H3 (mir-29c targets); and RUNX3, KLF5, IL1-β, and CTNNB1 (mir-375 targets) were correlated with basal-like and immune subtypes in QNBC patients and associated with a worse survival. Conclusion: Thus, QNBC tumors have an altered gene signature implicated in racial disparity and poor survival.

Background: Cancer-Related Fatigue (CRF) is a prevalent and debilitating symptom in breast cancer patients, significantly impacting their quality of life and potentially affecting postoperative outcomes. Despite advances in breast cancer treatment, the long-term implications of CRF on prognosis remain unclear. Methods: This retrospective cohort study included 310 postoperative breast cancer patients from two large comprehensive hospitals. We systematically collected demographic, medical history, lifestyle, psychological status, and CRF data. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Random forest survival analysis, propensity score matching, Kaplan-Meier survival analysis, and restricted cubic spline analysis were utilized to comprehensively evaluate the relationship between CRF and postoperative prognosis. Results: Higher CRF scores were associated with worse postoperative outcomes (HR = 1.07, 95% CI: 1.03-1.10, P < 0.001). Other independent prognostic factors included higher HADS scores (HR = 1.09, 95% CI: 1.01-1.17, P = 0.032), not undergoing breast-conserving surgery (HR = 0.43, 95% CI: 0.20-0.89, P = 0.024), and not receiving endocrine therapy (HR = 7.13, 95% CI: 2.64-19.22, P < 0.001). Random forest survival analysis highlighted CRF as the most critical variable impacting prognosis. Propensity score matching effectively balanced baseline characteristics, and Kaplan-Meier survival curves demonstrated significantly lower survival rates in high-CRF patients both before and after matching (P < 0.05). Restricted cubic spline analysis revealed a nonlinear relationship between CRF scores and disease progression risk, with significant risk increases beyond specific thresholds. Conclusions: CRF is a crucial predictor of disease progression in postoperative breast cancer patients. Higher CRF and HADS scores, non-breast-conserving surgery, and lack of endocrine therapy are associated with poorer prognosis. These findings underscore the importance of comprehensive postoperative care, including effective management of fatigue and psychological health, to improve patient outcomes. Future research should focus on prospective studies and targeted interventions for CRF to validate these findings and enhance clinical practices.

Breast cancer remains one of the most deadly non-communicable diseases in the world. The incidence of breast cancer in South Africa is increasing, with rural African women presenting with advanced stages of the disease. In this study, we aim to explore sociocultural factors influencing breast cancer screening practices among rural African women. A qualitative exploratory study was conducted using semi-structured interviews with 22 rural African women selected by purposive sampling. Thematic analysis was used to analyze the data. In this study, four sociocultural factors were identified as influencing breast cancer screening practices among rural African women. These factors included psychological factors, habits, beliefs, and healthcare perception. Women in rural African communities have deep-rooted traditional beliefs and practices regarding breast cancer. Consequently, this influences women's preventative health behaviours regarding breast cancer screening. To increase the number of women participating in breast cancer screenings, it is vital to develop culturally sensitive health education programs. Engaging community healers will also help to increase the number of women participating in breast cancer screening.

Background: Circulating tumor cells (CTC) have relevance as prognostic markers in breast cancer. However, the functional properties of CTCs or their molecular characterization have not been well-studied. Experimental models indicate that only a few cells can survive in the circulation and eventually metastasize. Thus, it is essential to identify these surviving cells capable of forming such metastases. Methods: We isolated viable CTCs from 50 peripheral blood samples obtained from 35 patients with advanced metastatic breast cancer using RosetteSepTM for ex vivo culture. The CTCs were seeded and monitored on plates under low adherence conditions and with media supplemented with growth factors and Nanoemulsions. Phenotypic analysis was performed by immunofluorescence and gene expression analysis using RT-PCR and CTCs counting by Cellsearch® system. Results: We found that in 75% of samples the CTC cultures lasted more than 23 days, predicting a shorter Progression-Free Survival in these patients, independently of having ≥ 5 CTC by Cellsearch®. We also observed that CTCs before and after culture showed a different gene expression profile. Conclusions: the cultivability of CTCs is a predictive factor. Furthermore, the subset of cells capable of growing ex vivo show stem or mesenchymal features and may represent the CTC population with metastatic potential in vivo.

To screen and validate immunosuppressive factors in luminal- and basal-like breast cancer cell lines and tissue samples associated with malignant phenotypes. The mRNA microarray datasets, GSE40057 and GSE1561, were downloaded and remodelled. Differentially expressed genes (DEGs) were identified. Enrichment analyses performed and the online resources, GOBO and Kaplan-Meier Plotter, were employed to screen for immunosuppressive factors associated with breast cancer malignant phenotypes. qRT-PCR and western blot were used to validate the expression of CD274 and IL8 in cell lines and immunohistochemical detected the MIF and VEGFA on tissue microarrays. The results showed that CD274 and IL8 were both upregulated in basal-like cell lines. That MIF expression was dramatically increased in patients with breast cancer metastases (p<0.05) and that VEGFA expression positively correlates with breast cancer pathologic grade (p<0.05).During the formation and development of breast cancer, immune-related genes are always activated, and immunosuppressive factors CD274, IL8, MIF and VEGFA are upregulated. Such molecules could be used as biomarkers for breast cancer prognosis. However, because individual immune-related factors can play several biological roles, the mechanistic relationship between immunosuppressive factors and breast cancer malignant phenotypes and the feasibility of their application as drug targets require further investigation.

Breast cancer is a global concern as a leading cause of death for women. Early and precise diagnosis can be vital in handling the disease efficiently. Breast cancer subtyping based on estrogen receptor (ER) status is crucial for determining prognosis and treatment. This study uses metabolomics data from plasma samples to detect metabolite biomarkers that could distinguish ER-positive from ER-negative breast cancers in a non-invasive manner. The dataset includes demographic information, ER status, and metabolite levels from 188 breast cancer patients and 73 healthy controls. Supervised, unsupervised, and ensemble machine learning (ML) algorithms were applied to identify key metabolites associated with ER status, including Support Vector Machines (SVM), Multidimensional Scaling (MS), Logistic Regression (LR), and Ensemble learning. The most informative feature set, containing 28 biomarkers and two demographic factors, achieved an impressive 96% accuracy and an area under the curve (AUC) of 93% using the Logistic Regression model. These results suggest that ML has great promise for identifying specific metabolites linked to ER expression, paving the development of a novel analytical tool that can minimize current lab challenges such as analytical sample handling, subjective results interpretation, biological heterogeneity of the tumor in a non-invasive and efficient manner aiding in more precise diagnosis of breast cancer.

Breast cancer is the foremost common in women, and its early diagnosis will help treat and increase patients' survival. This review article aims to studies on recent findings of standard imaging techniques and their characteristics for breast cancer diagnosis and recent nanoparticles (NPs) which are used for breast cancer detection. Herein, The search was performed in the literature through scientific citation websites, including Google Scholar, PubMed, Scopus, and Web of Science until May 2023. A comprehensive study on different imaging modalities and NPs for breast cancer diagnosis is reviewed, and their successes, challenges, and limitations are discussed.

Background: Circulating rare cells participate in breast cancer evolution as systemic components of the disease and thus, are a source of theranostic information. Exploration of cancer-associated rare cells is in its infancy. We determined the validity of a rare-cell detection platform and demonstrated the usefulness of a certain rare cell subset as a novel approach to characterize the breast cancer system. Methods: Linearity of the Rarmax® platform was established using a spike-in approach. The platform includes red blood cell lysis, leukocyte depletion and high-resolution fluorescence image recording. Rare cell analysis was conducted on 28 samples (before and after surgery) from 14 patients with breast cancer, 20 healthy volunteers and 9 non-cancer control volunteers. In-depth identification of rare cells, including circulating tumor cells, endothelial-like cells, erythroblasts and inflammation-associated cells, was performed using a phenotype and morphology-based classification system. Results: The platform performed linearly over a range of 5-950 spiked cells, with an average recovery of 84.6%. Circulating epithelial and endothelial-like cell subsets have been demonstrated to be associated with or independent of cancer with tumor presence. Furthermore, certain cell patterns may be associated with treatment-related adverse effects. The sensitivity in detecting tumor-presence and cancer-associated abnormality before surgery was 50% and 85.7%, respectively and the specificity was 100% and 96.6%, respectively. Conclusion: The present study supports the idea of a cancer-associated rare cell abnormality to represent tumor entities as well as systemic cancer. The latter is independent of the apparent clinical cancer.

Background/Objectives: The management of early breast cancer (BC) includes surgery, followed by adjuvant radiotherapy, chemotherapy, hormone therapy, or immunotherapy. However, the influence of these interventions in metabolic reprogramming remains unknown. This study explored alterations in the plasma metabolome of BC patients following distinct treatments to deepen our understanding of BC pathophysiology, outcomes, and the identification of potential biomarkers. Methods: We included 52 women diagnosed with BC and candidates for surgery as primary oncological treatment. Blood samples were collected at diagnosis, two weeks post-surgery, and one month post-radiotherapy. Plasma samples from 49 healthy women served as controls. Targeted metabolomics assessed 74 metabolites spanning carbohydrates, amino acids, lipids, nucleotide pathways, energy metabolism, and xenobiotic biodegradation. Results: Before treatment, BC patients exhibited notable changes in carbohydrate, nucleotide, lipid, and amino acid metabolism. We noticed a gradual restoration of specific metabolite levels (hypoxanthine, 3-phosphoglyceric acid, xylonic acid, and maltose) throughout different treatments, suggesting a normalization of nucleotide and carbohydrate metabolic pathways. Moreover, we observed increased dodecanoic acid concentrations, a metabolite associated with cancer protection. These variations distinguished patients from controls with high specificity and sensitivity. Conclusion: Oncological treatments modified the metabolism of patients towards a favorable profile with a decrease in the pathways that favor cell proliferation and an increase in the levels of anticancer molecules. These findings emphasize the pivotal role of metabolomics in recognizing the biological pathways influenced by each cancer treatment and the resulting metabolic consequences. Furthermore, it aids in identifying potential biomarkers for disease onset and progression.

Background and Objective: Type 2 diabetes mellitus (DM2) and breast cancer (BC) are diseases of high prevalence worldwide. Both alter lung function separately. So suffering both tables would increase this decrease in lung function. The objetive was to determine the effects of DM2 and BC on ventilation volumes and pressures in adult women. Material and Methods: Forty-two women patients were recruited, of whom 40 were accepted under the exclusion criteria. They were divided into four groups: control group (CG), DM2, BC and DM2+BC. Body plethysmography was used to measure forced vital capacity, lung volumes, airway resistance and muscle pressures. Finally the normality of the data was determined using Student's t test or the Mann-Whitney U test; the threshold of significance was p<0.05. Results: No significant differences were observed in the anthropometric variables between the control group and the other groups. The ventilation flows showed no significant differences, while the lung volumes presented significant differences in the inspiratory capacity (IC) variables (p<0,002). Maximum inspiratory and expiratory pressures (MIP-MEP) also presented significant diminution (p<0,001; p<0,041, respectively). Conclusions: From the results obtained we can conclude that the combination of type 2 diabetes mellitus with breast cancer caused a diminution in ventilation volumes and pressures, specifically in IC, MIP and MEP.

Matrix metalloproteases (MMPS) are a family of well-known enzymes which operate prevalently in the extracellular domain, where they fulfil the function of remodeling the extracellular matrix. Within the about 26 family members, encoded by 24 genes in humans, MMP-2 and MMP-9, have been regarded as the primary responsibility for the basement membrane and pericellular ECM rearrangement. In cases of infiltrating carcinomas, which arise from the epithelial tissues of a gland or of an internal organ, a marked alteration of the expression and the activity levels of both MMPs is known to occur. Present investigation represents the continuation and upgrading of our previous studies, now focusing on the occurrence and intensity levels of MMP-2 and -9, and their proteomic correlations, in a cohort of 80 breast cancer surgical tissues

This longitudinal study aimed to analyze the effects of a team rowing-based training program on physical fitness and anthropometric parameters in female breast cancer survivors (n=40; 56.78±6.38 years). Participants were divided into two groups: one rowed in fixed seat rowing (FSR) boats (n=20; 56.35±4.89 years) and the other in sliding seat rowing (SSR) boats (n=20; 57.20±7.7 years). Both groups engaged in two 75-minute sessions per week for 24 weeks. Significant improvements were observed in both groups in terms of weight (FSR: -1.93 kg, SSR: -1.75 kg), body mass index (FSR: -0.73 kg/m², SSR: -0.67 kg/m²), waist circumference (FSR: -2.83 cm, SSR: -3.66 cm), and hip circumference (FSR: -2.02 cm, SSR: -2.88 cm). Muscle strength improved in lower extremities (jump test: FSR: 2.99 cm, SSR: 3.11 cm) and upper extremities (dominant: FSR: 4.13 kgf, SSR: 4.34 kgf; non-dominant: FSR: 3.67 kgf, SSR: 3.32 kgf). Aerobic capacity also improved, with the SSR group showing a greater increase (FSR: 63.05 m, SSR: 93.65 m). Flexibility tests revealed better results in the SSR group for both dominant (SSR: 1.75 cm vs. FSR: -5.55 cm) and non-dominant limbs (SSR: 1.72 cm vs. FSR: -3.81 cm). These findings suggest that the type of rowing modality can influence physical fitness outcomes, with the SSR group showing superior improvements compared to the FSR group.

Introduction: Breast cancer affects worldwide almost 1.5 million women below the age of 45 years each year. Many of these women will be advised to undergo adjuvant chemotherapy to minimize the risk of death or recurrence of the tumor. For these patients, chemotherapy is a known cause of infertility, as it can damage primordial follicles which can lead to early menopause or premature ovarian insufficiency. This systematic review aims to synthesize the current evidence of the most suitable treatments for fertility preservation. Methodology: This review is performed following the PRISMA guidelines. The authors conducted an extensive search from the last 15 years. Relevant studies were pursued in PubMed, Embase and the Cochrane Library up until the July 31, 2023. A total of 7 eligible studies were identified. Discussion: The most suitable treatments for fertility preservation in young patients, is the temporary suppression with luteinizing hormone-releasing analogs, while the patient undergoes chemotherapy and cryopreservation. For cryopreservation, the physicians might deem it necessary to either cryopreserve ovarian tissue taken from the patient before any treatment or cryopreserve embryos/oocytes. Cryopreservation of oocytes and/or embryos is the most effective solution for fertility preservation in women of reproductive age, who have sufficient ovarian reserve and are diagnosed with breast cancer, regardless of the histological type of the tumor. Since approximately 50% of young breast cancer patients are interested in becoming pregnant right after completion of therapy, the evolution and development of fertility preservation techniques promise to be very exciting.

Bromodomain-containing protein 4 (BRD4) is an intracellular protein that regulates expression of various cellular functions. This study investigated whether BRD4 inhibition can alter the immunomodulatory and antitumor effects of radiation therapy (RT). A murine breast cancer cell line was implanted into BALB/c mice. The dual-tumor model was used to evaluate the abscopal effects of RT. A total of 24 Gy was delivered and BRD4 inhibitor was injected intravenously. Tumor size was measured and in vivo imaging was performed to evaluate tumor growth. Flow cytometry and immunohistochemistry were performed to examine immunologic changes upon treatment. The combination of BRD4 inhibitor and RT significantly suppressed tumor growth compared to RT alone. BRD4 inhibitor reduced the size of the unirradiated tumor indicating that it may induce systemic immune responses. Expression of HIF-1α and PD-L1 in tumor was significantly downregulated by the BRD4 inhibitor. Proportion of M1 tumor-associated macrophages (TAMs) increased, and proportion of M2 TAMs decreased upon BRD4 inhibition. BRD4 inhibitor expanded CD4+ and CD8+ T cell populations and reduced the population of monocytic myeloid-derived suppressor cells (M-MDSCs). RT-induced splenic M-MDSCs decreased upon addition of BRD4 inhibitor. Therefore, addition of BRD4 inhibition significantly enhanced the systemic antitumor responses of local RT.

Hypoxia, a condition of low oxygenation frequently found in triple-negative breast tumors (TNBC), promotes extracellular vesicle (EV) secretion and favors cell invasion, a complex process in which cell morphology is altered, dynamic focal adhesion spots are created, and ECM is re-modeled. Here, we investigated the invasive properties triggered by TNBC-derived hypoxic small EV (SEVh) in vitro in cells cultured under hypoxic and normoxic conditions, using pheno-typical and proteomic approaches. SEVh characterization demonstrated increased protein abundance and diversity over normoxic SEV (SEVn), with enrichment in pro-invasive pathways. In normoxic cells, SEVh promotes invasive behavior through pro-migratory morphology, in-vadopodia development, ECM degradation and matrix metalloprotease (MMP) secretion. Pro-teome profiling of normoxic cells exposed to SEVh determined enrichment in metabolic processes and cell cycle, modulating cell health to escape apoptotic pathways. In hypoxia, SEVh was re-sponsible for proteolytic and catabolic pathway inducement, interfering with integrin availabil-ity and gelatinase expression. Overall, our results demonstrate the importance of hypoxic signal-ing via SEV in tumors for the early establishment of metastasis.

Wnt pathway is involved in breast cancer (BC) progression. Our aim was to evaluate the expression of some components of the Wnt pathway (β-catenin, FZD4, LRP5, LRP6 and TCF1) in order to detect potential associations with NHERF1 protein. In addition, we assessed their impact on patients’clinical outcome. We evaluated 220 primary BC samples by immunohistochemistry (IHC) and protein localization by immunofluorescence. We found a significant correlation between NHERF1 and FZD4, LRP5, LRP6 and TCF1. Univariate analysis showed that β-catenin (p<0.0001), FZD4 (p=0.0001), LRP5, LRP6 and TCF1 over-expression (p<0.0001 respectively) was related to poor disease free survival (DFS). A Kaplan-Meier analysis confirmed univariate data and showed a poor DFS for cNHERF1+/FZD4+ (p=0.0007), cNHERF1+/LRP5+ (p=0.0002), cNHERF1+/LRP6+ (p<0.0001) and cNHERF1+/TCF1+ phenotypes (p=0.0034). In multivariate analysis, TCF1 and β-catenin expression were independent prognostic variable of worse DFS (p=0.009 and p=0.027, respectively). In conclusion, we found that β-catenin, FZD4, LRP5, LRP6 and TCF1 overexpression was associated to poor prognosis. Furthermore, we first identified TCF1 as independent prognostic factor of poor outcome, indicating it as a new potential biomarker for BC patients management. In addition, Wnt pathway proteins expression, both alone and in association with NHERF1, suggests original associations of biological significance for new studies.

Breast Cancer diagnosis is one of the most studied problems in the medical domain. In the medical domain, cancer diagnosis has been studied extensively which instantiates the need of early prediction of cancer disease. For obtaining advance prediction, health records are exploited and given as input to an automated system. This paper focuses on constructing an automated system by employing deep learning based recurrent neural network models. A stacked GRU-LSTM-BRNN is proposed in this paper that accepts health records of a patient for determining possibility of being affected by breast cancer. Proposed model is compared against other baseline classifiers such as stacked Simple-RNN model, stacked LSTM-RNN model, stacked GRU-RNN model. Comparative results obtained in this study indicate that stacked GRU-LSTM-BRNN yield better classification performance for predictions related to breast cancer disease.

The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The fragments were selected from patients with invasive ductal carcinoma of the breast, the most common and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers, useful for diagnostic and prognostic categorization of patients, in assessing post-surgical therapeutic regimes. The proteomic screening, by 2D-IPG and mass spectrometry, allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients, and proteins expressed sporadically among the same patients. Within the group of ubiquitous proteins, glycolytic enzymes and proteins with anti-apoptotic activity were predominant. Among the sporadic ones, proteins involved in cell motility, molecular chaperones and proteins involved in the detoxification appeared prevalent. The data of the present study indicates that the primary tumor growth is generally supported by two concurrent pathways: the inhibition of apoptosis and the stimulation of cellular proliferation. The second phase of the evolution of the tumor can be prematurely scheduled by the occasional presence of proteins involved in cell motility and in the defenses of the oxidative stress. To our knowledge this report on large-scales proteomics of breast cancer is currently a unique approach in the literature that offers the opportunity to evaluate the presence and recurrence of proteins to be used as prognostic indicators and susceptibility to metastasis in patients operated on for invasive ductal carcinoma of the breast.

Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence has accumulated suggesting a role for sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients with cancer and cancer survivors frequently experience poor sleep, manifested as insomnia, circadian misalignment, hypersomnia, somnolence syndrome, hot flushes, and nightmares. These problems are associated with a reduction in patients’ quality of life and increased mortality. Due to the heterogeneity among cancers, treatment regimens, patient populations, and lifestyle factors, the etiology of cancer-induced sleep disruption is largely unknown. Here, we discuss recent advances in understanding the pathways linking cancer and the brain and how this leads to altered sleep patterns. We describe a conceptual framework where tumors disrupt normal homeostatic processes, resulting in aberrant changes in physiology and behavior that are detrimental to health. Finally, we discuss how this knowledge can be leveraged to develop novel therapeutic approaches for cancer-associated sleep disruption, with special emphasis on host-tumor interactions.

Introduction: Depending on the kind of cancer and neurological disorders, there might be a direct or inverse link between neurodegeneration and cancer. The inverse interaction between cancer and Alzheimer's pathology has garnered substantial interest in medical research. While this inverse interaction between Alzheimer's pathology and cancer presents a fascinating scientific puzzle, there is still limited information and studies on the potential mechanisms involved in this inverse rela-tionship. Aim: This study aims to identify potential genes from Alzheimer's disease that may protect against cancer. Method: The Gene Expression Omnibus (GEO) database provided the Alzheimer's pathology dataset, and GEO 2R was utilized to examine genes that were differentially expressed. The expression of upregulated Alzheimer's pathology genes in breast, colorectal, and prostate cancer was compared using VENN 2.1, colorectal, and prostate cancer was compared using VENN 2.1, and colorectal and prostate cancers were compared using VENN 2.1. Results: Among the upregulated genes associated with Alzheimer's disease, 25 genes are shared among breast cancer, colorectal cancer, and prostate cancer, while 28 of these genes were exclusive to Alzheimer's dis-ease. Gene expression profiling interactive analysis among the shared genes revealed that AQP1, C4A, CSRP2, CRYAB, MACF1, HSPB2, and NEAT1 were downregulated in breast, colorectal, and prostate cancers. These genes have varying roles in cancer progression and suppression. Functional analysis of Alzheimer's disease-related upregulated genes revealed that C1orf56 and HIST1H2AC control cell proliferation, with HIST1H2AC playing a role in necroptosis. Additionally, C1orf56 worked as an oncogenic modifier to support DNMT3B's tumor suppressor properties. Conclusion: Given the role of HIST1H2AC and C1orf56 in the negative control of cell proliferation and their upregulation in Alzheimer's disease, there is a need to further investigate HIST1H2AC and C1orf56 as potential tumor suppressors responsible for Alzheimer's disease and cancer inverse association.

Purpose: The study aims to investigate racial disparities in fall-related injuries among Black and White breast cancer survivors who received chemotherapy, focusing on the risks associated with different chemotherapy regimens. Methods: This retrospective cohort study involved 11,400 breast cancer survivors (Stage 1-3) treated with chemotherapy between January 1, 2019, and December 31, 2023. Chemotherapy types studied include Doxorubicin, Cyclophosphamide, Paclitaxel, Docetaxel, and Carboplatin. Logistic regression and descriptive analyses were used to assess fall risk associated with each chemotherapy type, stratified by race. Results: The overall fall-related injury rate was higher among Black survivors (14.7%) compared to White survivors (10.0%), with a significant difference in fall risk between the two groups (p < 0.001). Fall risk was notably elevated for Black patients treated with Cyclophosphamide, Docetaxel, and Carboplatin. Conclusions: The findings highlight significant racial disparities in fall-related injuries among breast cancer survivors receiving chemotherapy. These disparities may be influenced by socioeconomic factors and healthcare access. Implications for Cancer Survivors: Interventions targeting fall prevention and equitable healthcare access are critical to reducing these disparities among Black breast cancer survivors.

Breast cancer is a complex and heterogeneous disease that displays diverse molecular subtypes and clinical outcomes. Although it is known that the location of tumors can affect their biological behavior, the underlying mechanisms are not fully understood. In our previous study, we found a differential methylation profile and membrane potential between left (L) and right (R)-sided breast tumors. In this current study, we aimed to identify the ion channels responsible for this phenomenon and determine any associated phenotypic features. To achieve this, experiments were conducted in mammary tumors in mice, human patient samples, and with data from public datasets. The results revealed that L-sided tumors have a more depolarized state than R-ones. We identified a 6-ion channel-gene signature (CACNA1C, CACNA2D2, CACNB2, KCNJ11, SCN3A, and SCN3B) associated with side: L-tumors exhibit lower expression levels than R-ones. Additionally, in silico analyses show that the signature correlates inversely with DNA methylation writers and with key biological processes involved in cancer progression, such as proliferation and stemness. The signature also correlates inversely with patients’ survival rates. In an in vivo mouse model, we confirmed that KI67 and CD44 markers were increased in L-sided tumors and similar tendency for KI67 was found in patient L-tumors. Overall, this study provides new insights into the potential impact of anatomical location on breast cancer biology and highlights the need for further investigation into possible differential treatment options.

PIK3CA is a gene usually mutated in breast cancer and has an important role in tumor progression and treatment. Therefore, there is required a technique to detect low-rate PIK3CA mutations improving the clinical conduct. This study aimed to compare chip-based dPCR and Sanger sequencing to detect PIK3CA mutations in breast cancer patients. Fifty-seven tumor samples from breast cancer patients were collected and analyzed by Sanger sequencing and dPCR for PIK3CA mutations (E545K, H1047R, and H1047L). Digital PCR sensitivity, specificity, and overall performance were estimated by contingency tables, receptor operator characteristic (ROC), and area under the curve (AUC). Sanger sequencing identified PIK3CA mutations in six patients (10.5%), two with H1047R, and four with E545K. Digital PCR confirmed those mutations and identified 19 additional patients with at least one mutation. Comparison between dPCR and Sanger sequencing showed a sensitivity of 100% (95% CI 53-100%), and a specificity of 84.2% (95% CI 83 - 84.2%). Besides, H1047R mutation showed a significant association with breast cancer phenotype (p =0.019) and lymphatic node infiltration (p =0.046). Digital PCR showed a high sensitivity to detect mutations in tumor samples and it might be capable to detect low-rate mutations and tumor subpopulations not detected by Sanger sequencing.

Aims: To assess the occurrence of Chemotherapy-induced nausea and vomiting (CINV) after standard antiemetic therapy in the acute (24 h post-chemotherapy) and delayed (2–5 days post-chemotherapy) phases, as well as to identify risk factors for CINV in the acute and delayed phases. Methods: This prospective longitudinal and observational study analyzed the data of 400 breast cancer patients scheduled for chemotherapy over two cycles in two hospitals. The self-report survey was developed to assess the occurrence of CINV and their associated factors. CINV was evaluated with a Multinational Association of Supportive Care in Cancer Antiemetic Tool (MAT) on days 2 and 6 of chemotherapy. The incidence of acute and delayed CINV were presented by frequency and percentage. Generalized equation estimates (GEE) was used to identify risk factors of acute and delayed CINV. Results: There were 400 evaluable patients with complete Round 1 data, 334 for Round 2 data. Among 400 patients, 29.8% and 23.5% experienced acute and delayed CINV, respectively. Risk factors associated with for acute CINV were pain/insomnia, history of CINV, history of motion sickness (MS), and highly emetogenic chemotherapy regimen, while history of MS, CINV history, number of completed chemotherapy cycle number < 3, and the incidence of acute CINV were risk factors of delayed CINV (all p < 0.05). Conclusions: The findings may help nurses working for Chinese population in identifying patients at risk for CINV and in planning effective program to reduce the occurrence of CINV.

Chemotherapy-related deaths, the result of treatment with faulty medications, account for nearly 10% of all breast cancer deaths (Rashbass, 2016). Patient-specific, personalized medicine is evidently required to administer optimized therapeutics and prevent treatment-related mortality. In order to develop a predictive model for breast cancer therapy, the following study analyzed the mRNA data of 4,704 genes derived from 20 breast cancer patients before and after doxorubicin treatment for 16 weeks (O’brien et al., 2006; Perou et al., 2000). The genomic data of each patient was first stratified into 9 groups (corresponding to the 9 Mechanisms defined in Figure 4) based on mRNA expression in response to the tumor and to the doxorubicin treatment. The study then employed the Planckian Distribution Equation (PDE) discovered at Rutgers University to model the stratified samples by transforming each mechanism into a single long-tailed histogram fitted by the PDE. Our PDE model is based on 3 parameters - A, B, and C - of which 2 were extracted from each model to generate the plots seen in figures 5e and 5f. The drug-induced slopes of the A vs C plots were then determined for all 9 mechanisms of each patient. The study observed an increase in post-treatment mRNA levels for longer surviving patients in 6 mechanisms. Further analysis displayed how the drug treatment uniquely altered each of the mechanisms based on the length of patient survival. These results indicate that the PDE-based procedures described herein may provide a novel tool for discovering potential anti-breast cancer pharmaceuticals.

Even with 100% certainty of a complete cure for breast cancer (BC), there is still a long way to go toward more efficient treatment. This requires sensitive and timely detection and accurate pre/post-clinical characterizations. Despite the availability of advanced diagnostic tools, many cancer patients lack access to efficient diagnostics that are both highly reliable and affordable. The fluorescence-based optical technique aims to make another significant leap forward in improving patient safety. It offers a convenient operation that reduces healthcare costs compared to visual examination tools (VETs). The primary and metastatic stages of BC consider different cancerous cell lines (MDAs), meaning the highest number of cells in this research (up to 300,000) represents the metastatic stages of BC, and 50,000 represents the primary level of BC developments have been studied based on fluorescence-enhanced photodynamic characterizations. The ability to characterize the fluorescence caused by MDA with 50,000 cells compared to the dominant radiation of MDA with 300,000 cells is emphatic proof of the high potential of fluorescence technique in timely BC detections, specifically before it spreads to the axillary lymph nodes. The specific cell numbers of 50,000 and 300,000 were chosen arbitrarily based on the cultivation of common biological limitations. Comparing the outcomes between 50,000 and 300,000 cells allows for evaluating the fluorescence technique’s diagnostic capability across various stages of breast cancer. This assessment provides valuable insights into the effectiveness of the fluorescence-based characterizing approach in detecting cancerous cells at different stages of the disease. Here, we have assessed fluorescence’s spectral shift and intensity difference as a diagnostic approach to distinguish between cancerous and normal breast cells. This study also presents a two-way structure of the 5-aminolevulinic acid (5-ALA) prodrug and Fluorescein Sodium (FS) effect in BC cell characterization from the perspective of photodynamical procedures and the detection side. 5-ALA induces an accumulation of protoporphyrin IX (PpIX) photosensitizer through a biosynthetic pathway, leading to red radiation of fluorescence measurements depending on different factors, such as temperature, incubation time, added glucose of the culturing medium, as well as photosynthesis processes. The presence and progression of breast cancer can be indicated by elevated levels of Reactive Oxygen Species (ROS), which are associated with the production of PpIX in cells following the administration of 5-ALA. Also, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) fluorophores are recognized as the main factors for fluorescence emissions at around 420-580 nm emission intervals. Considering the MDA’s high metastatic potential, the impact of 5-ALA on MDA’s cellular morphology and viability has been investigated. The molecular fluorophores are the primary probes to MDA’s cellular photodynamic considerations, allowing this widespread pre/post-clinical approach. The fluorescence signal reduction due to decreased cell viability and increased MDA’s cellular death rate after 24 hours of the 5-ALA-induced staining corresponds to the changes in lipid metabolism enzymes of MDAs cultured at different doses, which could be known as a cell death inducer function. Furthermore, statistical concerns have been studied using PCA multivariate component analysis to differentiate MDA cell lines administrated by 5-ALA.