Breast Cancer Research Articles

Unlocking survival benefits: primary tumor resection in de novo stage IV breast cancer patients

ABSTRACT Background For patients with de novo stage IV breast cancer (BC), the conditions under which the primary tumor resection (PTR) may offer benefit remain unclear. Methods The SEER database provides treatment data for patients with de novo stage IV BC. We screened cases of metastatic BC diagnosed from 2010 to 2015, with primary endpoints of overall survival (OS) and cancer-specific survival (CSS). Results 9252 patients with stage IV de novo BC were enrolled. For OS, median survival time (MST) was 38 months with systematic treatment (ST) compared to 52 months with ST plus PTR (p < 0.001). For CSS, MST was 38 months for ST versus 54 months for ST plus PTR (p < 0.001). The results of the Cox proportional hazards regression analysis regarding PTR, for OS: bone metastasis (aHR 0.664, 95%CI 0.583–0.756, p < 0.001); liver-lung metastasis (aHR 0.528, 95%CI 0.327–0.853, p = 0.009). For CSS: bone metastasis (aHR 0.655, 95%CI 0.571–0.751, p < 0.001); liver-lung metastasis (aHR 0.549, 95%CI 0.336–0.889, p = 0.017). Kaplan-Meier analysis indicated that in patients with bone metastases and liver-lung metastases, PTR could improve survival outcomes. Conclusion Liver-lung metastases and bone metastases in patients with de novo stage IV BC could enhance both OS and CSS through PTR.

Patient-reported persistent lymphedema and peripheral neuropathy among long-term breast cancer survivors in theCarolina Breast Cancer Study.

Improved breast cancer treatment has lengthened survival but also has long-term impacts. Lymphedema and peripheral neuropathy are treatment-related sequelae that extend into survivorship. Co-occurrence of these conditions may further impair functional well-being. Few studies have estimated the burden of these conditions among diverse survivors. Carolina Breast Cancer Study Phase 3 enrolled survivors diagnosed between 2008 and 2013 in North Carolina. Black and younger women (aged <50 years at diagnosis) were oversampled. With the use of ≥10 years of follow-up data, the prevalence of persistent lymphedema, peripheral neuropathy, and their co-occurrence was assessed. Prevalence differences (PDs) and 95% confidence intervals (CIs) were assessed according to patient and disease characteristics. A total of 1688 survivors were included, with an average of 11.1 years (SD, 0.6) postdiagnosis. The prevalence of persistent lymphedema, peripheral neuropathy, and their co-occurrence was 18.7%, 27.7%, and 8.8%, respectively. Lymphedema was higher among those receiving a mastectomy and with >5 lymph nodes removed, and peripheral neuropathy was higher among women treated with taxane-based chemotherapy. Co-occurrence was higher among women with >5 lymph nodes removed (vs. <5; PD, 5.4; 95% CI, 2.1 to 8.8) and those treated with taxane-based chemotherapy (vs. no chemotherapy; PD, 6.8; 95% CI, 3.9 to 9.7). The burden of lymphedema (PD, 2.7; 95% CI, 0.9 to 6.3) and peripheral neuropathy (PD, 5.8; 95% CI, 1.7 to 9.9) was higher among Black than White women. The prevalence of lymphedema (PD, 1.8; 95% CI, -1.5 to 5.1) and peripheral neuropathy (PD, 4.6; 95% CI, 0.8 to 8.4) was elevated among younger compared to older women. Lymphedema and peripheral neuropathy affect a substantial proportion of survivors. Interventions are needed to reduce this burden.

Effects on lymph node size, staging and primary tumor histology on diagnostic accuracy of axillary lymph node aspirate of breast cancers.

Fine-needle aspiration cytology is preferred for axillary lymph node metastasis with low costs and minimal risks. To improve diagnostic performance by incorporating clinical-radiological-pathological parameters, a large cohort pre-operative aspirates in were reviewed for parameters affecting adequacy rate and accuracy. Axillary nodal aspirates from three institutions with histologic correlation were retrieved. Case notes were reviewed for parameters pertaining to the primary tumor, nodal status, histologic and cytologic diagnoses. Totally 1361 specimens were included. The risk of malignancy for C1-C5 categories were 53.39%, 27.45%, 70.97%, 83.33% and 88.00%, increasing to 75.86%, 94.59% and 99.28% for C3/C4/C5 categories excluding cases with neoadjuvant therapy. Node size (p < 0.001) and histologic grade (p = 0.003) of primary tumor positively correlated with specimen adequacy. Presence of in situ component trended towards inadequacy (p = 0.069). Lymph node size remained a strong predictor of concordant cytologic diagnosis (p < 0.001). A higher percentage of involved node (p = 0.006) and HER2 overexpressed breast cancers (p = 0.027) increased concordance. Cases with ≥ 4 (up to ≥ 10) positive nodes were more likely to be concordant (p = 0.009- < 0.001), with improvements of 8.27%-12.37%. For size, cut-offs of ≥ 5 and ≥ 10mm were significant (p = 0.006- < 0.001). It is critical that clinical-radiological-pathological findings be interpreted together with cytology. Aspirates from smaller nodes are more likely to be non-informative, irrespective of the total number of suspicious nodes, or a high-grade primary. In axillae with less than 4 suspicious nodes and/or a target node of less than 5-10mm, the diagnostic accuracy of aspiration cytology decreases and should be interpreted cautiously.

Synthesis of liposomal nanoparticles to load 4-farnesyloxycoumarin and investigating its anti-cancer and anti-metastatic effects.

The aim of this study was to load 4-farnesyloxycoumarin (4-FLC) in nanoliposomes (4-FLC-LNPs) and evaluate its anti-cancer and anti-metastatic effects. 4-FLC-LNPs were synthesized using a combination of lecithin-cholesterol-polyethylene glycol. The physicochemical properties were evaluated using DLS, FTIR, and microscopy methods. The toxicity against breast cancer (MCF-7), prostate cancer (PS3), pancreatic cancer (PANC), gastric cancer (AGS), and normal cell lines (HUVEC) was evaluated using the MTT assay. Fluorescent staining and flow cytometry were used to assess the occurrence of apoptosis. Molecular analysis methods were used to study the apoptosis and metastasis effects of these nanoliposomes. The antioxidant power of 4-FLC-LNPs was measured using the ABTS and DPPH free radicals methods. 4-FLC-LNPs exhibit a spherical morphology, with an average size of 57.43 nm, a polydispersity index of 0.29, and a zeta potential of -31.4 mV. They demonstrate an encapsulation efficiency of 82.4% for 4-FLC. The IC50 value of 4-FLC-LNPs against the breast cancer cell line was reported as the most sensitive, at approximately 60 μg/mL. ABTS and DPPH results were reported at approximately 30 µg/mL. The inductive effects of nanoliposomes on the apoptosis process were confirmed by an increase in the number of apoptotic cells, as well as the arrest of cells in various phases of cell growth. The increased expression of BAX and decreased expression of Bcl-2, MMP-2, and MMP-9 confirmed the pro-apoptotic and anti-metastatic effects of 4-FLC-LNPs. These finding validate the therapeutic potential of 4-FLC-LNPs, which may be utilized in preclinical studies.

Factors associated with breast cancer detection method in California women: an analysis of California Health Interview Survey data.

Breast cancer mortality has significantly declined in the U.S. due in part to effective clinical screening methods. However, previous studies have found many women first detect their breast cancers through means other than their providers. Given that detection method has been shown to be an important prognostic factor, we examined the association between breast cancer detection method and various demographic and health-related factors in a representative sample of female breast cancer patients aged 40 + in California. We analyzed data from the 2009 and 2011-2012 California Health Interview Survey. Weighted percentages of breast cancer patients by detection method were calculated. A multivariable logistic regression model was used to quantify each factor's association with the likelihood of having a patient-detected versus clinically detected breast cancer using odds ratios (ORs) and 95% confidence intervals (CIs). 36% of female breast cancer patients first detected their cancer themselves. Compared to U.S.-born women, those who had spent 40% or less of their lifetime in the U.S. were more than twice as likely to report their breast cancer being patient-detected versus clinically detected (OR = 2.27, 95% CI 1.06-4.86, p = 0.035). Rural women were also more likely to report a patient-detected breast cancer than urban women (OR = 1.51, 95% CI 1.01-2.11, p = 0.044). Recent immigrants and those residing in rural areas were more likely to report self-detecting their breast cancer. Given the persistent disparities with regard to breast cancer mortality, particularly among underserved communities, strategies addressing barriers to screening uptake in these populations may be warranted.

Unveiling the therapeutic potential of anthocyanin/cisplatin-loaded chitosan nanoparticles against breast and liver cancers

Abstract Background Liver and breast cancers are among the leading causes of cancer-related deaths worldwide, prompting researchers to seek natural anticancer agents and reduce chemotherapy side effects. Red beetroot (Beta vulgaris Linnaeus), rich in polyphenols and powerful antioxidants, has shown potential in cancer prevention. This study aimed to evaluate the impact of red beetroot-derived anthocyanin (Ant), Ant-loaded chitosan nanoparticles (Ant NPs), cisplatin (Cis), Cis-loaded chitosan (Cis NPs), and Cis + Ant-loaded chitosan NPs on human hepatoma HepG2 and breast adenocarcinoma MCF7 cell lines. Methods NPs preparation was evaluated by zeta potential, FTIR, and SEM. The cytotoxic, apoptotic, antioxidant, anti-inflammatory, anti-metastatic, and anti-angiogenic effects were assessed by MTT assay, qPCR, AO/EB staining, and flow cytometry. Results Treatment with Ant, Ant NPs, Cis, Cis NPs, and Cis + Ant NPs caused cytotoxicity in HepG2 and MCF7 with best effect in Cis-treated cells. The anticancer effects were attributed to mitochondrial-dependent apoptosis (with high Bax and low Bcl2 expression), chromatin disintegration, and cell cycle arrest in G2/M and S phases. All treatments inhibited migration by downregulating the migration-related gene MMP9 and upregulating the anti-migratory gene TIMP1 and decreased the angiogenesis-related gene VEGF and the inflammatory gene TNFα with best results in Cis NPs-treated cells. Interestingly, Ant, Ant NPs, and Cis + Ant NPs increased the antioxidant status (high GSH and upregulated expression of Nrf2 and OH-1) and decreased drug resistance-related MAPK1 and MDR1 genes compared to Cis and Cis NPs-treated cells. Conclusions Anthocyanin and cisplatin-loaded chitosan nanoparticles effectively combat breast and liver cancers by inducing cancer cell apoptosis, enhancing antioxidant defenses, and reducing inflammation. They also inhibit tumor spread and blood vessel formation through downregulation of MMP9 and VEGF, highlighting their therapeutic potential.

Single-cell expression and immune infiltration analysis of polyamine metabolism in breast cancer.

Breast cancer is one of the most threatening women health diseases worldwide and its molecular heterogeneity offers a range of response to therapy. The role of polyamine metabolism is receiving increasing attention. Polyamine metabolism not only plays an important role in the occurrence and development of breast cancer, but also interacts with tumor immune microenvironment. In this work, we applied single-cell RNA-sequencing (scRNA-seq) and systems immunological approaches to interrogate immune cell infiltration gene-to-gene co-expressions in the bulk tumor transcriptomes of breast cancer. We acquired breast cancer sample data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), evaluated the infiltration status of 22 immune cell types using CIBERSORTx tool, respectively. By leveraging the Retrospective Breast sample of various technologies including gene expression and methylation, we identified 46 breast cancer proliferation-associated co-expression modules using weighted gene coexpression network analysis (WGCNA) approach along with machine learning models which in turn delineated single cell level expressions features that these selected module possessed. We observed substantial cellular heterogeneity in the breast cancer microenvironment, where lineage-specific gene expression patterns were highly associated with tumor progression. Moreover, we also identified the gene modules correlated with immune cell infiltration level that could function as regulators in response to tumors for immune therapy. Moreover, risk scores were correlated with immune cell function in different patient groups defined by high- and low-risk. The findings of this study shed a new light upon molecular classification prognostic assessment and personalized treatment in breast cancer.

Unleashing the potential of Genistein and its derivatives as effective therapeutic agents for breast cancer treatment.

Breast cancer remains one of the leading causes of cancer-related deaths among women worldwide. Genistein (Gen), a phytoestrogen soy isoflavone, has emerged as a promising agent in the prevention and treatment of breast cancer due to its ability to function as a natural selective estrogen receptor modulator (SERM). This review explores the multifaceted mechanisms through which Gen and its derivatives exert their anticancer effects, including modulation of the PI3K/Akt signaling pathway, regulation of apoptosis, inhibition of angiogenesis, and impacts on DNA methylation and enzyme functions. We discuss the dual roles of Gen in both enhancing and inhibiting estrogen receptor (ER)-dependent pathways., highlighting its complex interactions with ERα and ERβ. Furthermore, the review examines the synergistic effect of combining Gen with conventional chemotherapeutic agents such as doxorubicin, cisplatin, and selenium, as well as other natural compounds like lycopene. Clinical studies suggest that while isoflavones may not significantly influence breast cancer progression in general, the high consumption of soy isoflavones is associated with reduced recurrence rates in breast cancer survivors. Importantly, Gen's ability to modulate key signaling pathways and enhance the efficacy of existing treatments improves its potential as a valuable adjunct in breast cancer therapy. In conclusion, Gen and its derivatives offer a novel and promising approach for treatment of breast cancer. Continued research into their mechanisms of action and clinical applications will be essential in optimizing their therapeutic potential and translating these findings into effective clinical interventions.

Oxidative stress drives endometrial fibrosis via TGF-β1/MAPK signaling pathway in breast cancer.

Breast cancer patients have high serum reactive oxygen species (ROS) levels, which exert toxicity on the ovary. However, it is still unclear whether tumor-derived ROS play a role in endometrial development and function in breast cancer. Breast cancer patients and healthy controls were recruited and endometrial thickness was measured by transvaginal ultrasound (TVUS). Xenograft tumors of the breast cancer cell line MDA-MB-231 in a female BALB/c nude mice model were established, and the therapeutic mechanism of vitamin C (VC) was investigated on uterine pathology invivo and the contribution of co-culture of breast cancer cell and endometrial epithelial cell on this process was examined invitro. Median thickness in endometria was lower in breast cancer patients and tumor-bearing mice compared to controls. A gene signature of uteri in tumor-bearing mice demonstrated differential expression of genes (DEGs) regulating extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT), and activation of TGF-β and MAPK signaling pathways. In addition, ROS, EMT- and ECM-related protein levels were enhanced in uteri in tumor-bearing mice, as well as in Ishikawa cells which were co-cultured with MDA-MB-231 cells compared to controls. Supplementation with VC reduced endometrial damage, inhibited the EMT process and collagen deposition, and maintained better histologic architecture of uteri in tumor-bearing mice via inactivation of the TGF-β1/p38MAPK pathway. In women with breast cancer oxidative stress in the endometrium results in a fibrotic response as a consequence of EMT. VC could alleviate endometrial fibrosis via TGF-β1/p38MAPK pathway and provide new predictive and therapeutic targets for fertility preservation in younger breast cancer patients.

FATS inhibits the Wnt pathway and induces apoptosis through degradation of MYH9 and enhances sensitivity to paclitaxel in breast cancer.

Breast cancer is one of the most prevalent and diverse malignancies, and, with global cases increasing, the need for biomarkers to inform individual sensitivity to chemotherapeutics has never been greater. Our retrospective clinical analysis predicted that the expression of the fragile site-associated tumor suppressor (FATS) gene was associated with the sensitivity of breast cancer to neoadjuvant chemotherapy with paclitaxel. In vitro experiments subsequently demonstrated that FATS significantly increased the inhibitory effects of paclitaxel on breast cancer cells' migration, growth, and survival. An interaction screen revealed that FATS interacted with MYH9 and promoted its degradation via the ubiquitin-proteasome pathway, thereby downregulating Wnt signaling. By overexpressing FATS and MYH9, we demonstrated that FATS enhanced paclitaxel-induced apoptosis in breast cancer cells by degrading MYH9 to downregulate the Wnt pathway. We also demonstrated in a mouse xenograft model that FATS significantly increased the chemosensitivity of breast cancer cells to paclitaxel in vivo. This study presents a new mechanism by which FATS interacts with MYH9 to suppress the Wnt/β-catenin signaling pathway and induce apoptosis, thus enhancing the sensitivity of breast cancer cells to paclitaxel chemotherapy. The results also propose novel biomarkers for predicting breast cancer sensitivity to neoadjuvant chemotherapy with paclitaxel. Finally, we provide in vivo evidence that the combination of paclitaxel with IWR-1, a novel Wnt pathway inhibitor, synergistically suppresses breast cancer growth, laying the foundation for future trials with this drug combination. These results therefore provide a number of potential solutions for more precise treatment of patients with breast cancer in the future.

PLLA Porous Scaffold as a 3D Breast Cancer Model to Investigate Drug Resistance.

Multidrug resistance remains one of the major challenges in breast cancer research, often leading to treatment failure. To better understand this mechanism, sophisticated three-dimensional (3D) tumor models are necessary, as they offer several advantages over traditional bidimensional (2D) cultures. In this study, poly-l-lactic-acid porous scaffolds were produced using a thermally induced phase separation technique and employed as 3D models for breast cancer cell lines: MDA-MB-231, MCF-7, and its multidrug-resistant variant, MCF-7R. The MTS assay was used to compare growth inhibition following doxorubicin treatment in 2D and 3D. Remarkably, the IC50 values increased in 3D cultures compared to 2D: MDA-MB-231 (445 vs. 54.5 ng/mL), MCF-7 (7.45 vs. 0.75 μg/mL), and MCF-7R (165 vs. 39 μg/mL). MCF-7R, which usually shows greater resistance in 2D, demonstrated even higher resistance in 3D. In fact, IC50 was not reached within 3 days as with the other models, but only after 6 days. Cellular morphology also played a crucial role. When treated with concentrations higher than the IC50, MDA-MB-231 cells lost their physiological 3D clustered structure, while MCF-7 and its resistant variant exhibited disrupted layers. All cell lines in 3D showed higher chemoresistance, suggesting a more biomimetic spatial architecture. Our work bridges the gap between monolayer and animal models, highlighting the potential of polymeric 3D scaffolds in breast cancer research.

Comprehensive characterization of invasive mammary carcinoma with lobular features: integrating morphology and E-cadherin immunohistochemistry patterns.

Breast cancer treatment prioritizes molecular subtypes over histologic types. However, considering the unique biological behavior of invasive lobular carcinoma (ILC), its diagnosis is crucial for patient management. Therefore, this study aimed to review breast cancer cases, focusing on the E-cadherin patterns and lobular morphology of cases misclassified in the original reports. A comprehensive review was conducted on 481 breast cancer biopsy cases diagnosed as invasive breast carcinoma of no special type (IBC-NST) or ILC with E-cadherin staining. These cases were categorized into six groups based on tumor morphology (ductal/lobular) and E-cadherin expression pattern (membranous/loss/aberrant): (1) ductal/membranous, (2) lobular/loss, (3) lobular/aberrant, (4) mixed, (5) ductal/loss or aberrant, and (6) lobular/membranous. In 211 cases (43.8%), an E-cadherin pattern indicating ILC (loss and aberrant) was observed alongside lobular morphology, representing 5.52% of all breast cancer biopsies during the relevant period. Moreover, 181 cases (37.6%) showed a membranous pattern with ductal morphology, 4 (0.8%) were mixed IBC-NST and ILC, and 85 (17.7%) exhibited discordance between morphology and E-cadherin expression. Notably, only 25.9% (15/58) of cases in group 3, characterized by aberrant E-cadherin patterns, were initially diagnosed as ILC, highlighting a significant diagnostic discrepancy. In group 6, where membranous E-cadherin pattern was present with lobular morphology, only 3.4% (2/58) were diagnosed as ILC in the original reports, indicating diagnostic challenges in morphology and immunohistochemistry discordance. Similarly, in group 5, which had ductal morphology with loss or aberrant E-cadherin expression, the initial diagnosis rate of IBC-NST was 33.3% (9/27), reflecting the complexities in interpreting discordant cases. In real-world practice, diagnosing ILC often heavily depends on E-cadherin results. This study emphasizes the need for diagnostic clarification in cases with discordance between morphology and E-cadherin patterns.

Metamaterial-based Artificial magnetic conductor for efficient breast cancer diagnosis using a low-cost antenna array.

Breast cancer is the most common malignancy in women globally, stemming from gene mutations that prompt irregular cellular growth and subsequent tumor development. Early-stage detection of cancer cells results in a remarkable 99% survival rate. This research presents a microwave imaging technique for the non-invasive identification of tumors in the initial stages within the women's breast. A low-cost antenna array with an Artificial Magnetic Conductor (AMC) is proposed, featuring a compact structure size of 37.2 37.2 mm . The AMC, a metamaterial, acts as a reflective surface to enhance frequency selectivity, specifically at 8.48 GHz. The maximum gains reached 9.35 dBi in simulated results and 10.51 dBi in measured results. The fabricated antenna validates the simulated findings, and its operational efficiency has undergone experimental validation. Moreover, fidelity factors in face-to-face (FtF) and side-by-side (SbS) scenarios are delineated. The antenna, operating as a transceiver, is applied to a modeled breast phantom across five distinct cases for numerical simulations pertaining to cancer cell detection applications. The outcomes of this research bear considerable implications for advancing early-stage breast cancer detection methodologies.

An educational approach using interprofessional (IP) role plays and patient narratives to inculcate empathy and communication among undergraduates in breast cancer management.

Interactive teaching methods such as patient narratives and role plays are effective tools in medical education. Incorporating the patient's perspective of the disease and standardized treatment in the teaching process helps the students become more empathetic and have better doctor-patient communication. An interactive module was conducted using role plays and patient narratives to teach communication skills and doctor-patient relationships to randomly chosen Seventy-seven final-year(4thyear) medical students to address the various psychosocial problems faced by the patients with breast cancer. Participants' perspectives regarding the intervention were collected using pre and post-tests, session feedback, and interviews. The data were analyzed quantitatively and qualitatively, as appropriate. Observed Structured Clinical Examination (OSCE)stations with case scenarios to break bad news to simulated patients were used for the assessment. Most participants felt that such interactive sessions were needed where they played the role of a doctor before facing an actual patient. While reading the narratives, they felt that the narrators' emotions were genuine and that they felt involved. Most of them could relate to the social and emotional aspects of the patient and understood the Interprofessional (IP) teamwork in the treatment of a breast cancer patient. 93.4% of the participants felt they gained competence in managing difficult communication situations with patients. Interactive teaching methods like narratives and role play may help enhance students' communication and empathy, which is vital for future doctors. They seamlessly integrate into existing curricula, offering practical experiences that deepen understanding and empathy without disrupting learning.

Real-world application of disitamab vedotin (RC48-ADC) in patients withbreast cancer with different HER2 expression levels: efficacy and safety analysis.

Disitamab vedotin (RC48-ADC), an antibody-drug conjugate (ADC), combines specific antibody disitamab with cytotoxicity monomethyl auristatin E to effectively target the human epidermal growth factor receptor 2 (HER2) protein on tumor cells for precise elimination. Recent studies have demonstrated that RC48-ADC offers therapeutic benefits for patients with HER2-positive and HER2-low-expression breast cancer (BC). However, a thorough exploration of its efficacy and safety in real-world settings for patients with metastatic breast cancer (mBC) is currently lacking. This retrospective, multicenter, real-world study included patients with mBC who received RC48-ADC from September 2021 to March 2024. These patients include HER2-positive BC and HER2-low-expression BC. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), restricted mean survival time, objective response rate (ORR), and disease control rate (DCR). Factors affecting efficacy and the occurrence of treatment-related adverse events (TRAE) were evaluated. The study included a cohort of 89 patients with mBC, with 48 of those being identified as HER2-positive. As of March 2024, 22 deaths were recorded, with an immature median OS. Total PFS varied from 1.0 to 31.2 months, with a median of 5.5 months (95% CI, 4.368-6.632). HER2-positive patients exhibited prolonged PFS compared with HER2-low-expression patients (6.6 months vs 4.1 months, P = .023). The overall ORR stood at 25.8% (95% CI, 0.178-0.358), with higher rates observed in HER2-positive patients compared with HER2-low-expression patients (31.3% vs 19.5%). Similarly, the overall DCR was 78.7% (95% CI, 0.691-0.859), with HER2-positive patients demonstrating superior DCR compared with HER2-low-expression patients (83.3% vs 73.2%). Notably, HER2 expression emerged as the primary determinant of RC48-ADC efficacy. The most prevalent TRAE among all patients included leukopenia (21.3%) and alopecia (20.2%). RC48-ADC showcases promising efficacy and manageable safety in patients with both HER2-positive and HER2-low-expression mBC.

The Integrative Single-Case Design as a Biosemiotic-Systemic Research Tool in Psychoneuroimmunology.

Psychoneuroimmunology (PNI) is a field of research that deals with the interactions between psyche, nervous, endocrine, and immune systems. Investigating these complex PNI relationships under asecologically validas possible conditions ("life as it is lived") necessitates a paradigm change in research. This shift placesfactors such as "time" and "subjective meaning" of personal experiences at the center of the research methodology. For this purpose, the biosemiotic-systemic research design "Integrative Single-Case Study" was developed. Initial results from healthy individuals as well as patients with systemic lupus erythematosus (SLE), breast cancer, and rheumatoid arthritis(RA) support the validity of the research approach. Specifically, in connection with the occurrence ofemotionally meaningful everyday incidents, we repeatedlyobserved stress system reactions, which were(1) delayed over several days, (2) cyclically patterned, (3) anticipatory, and (4) opposing, depending on a)whether participants experienced emotionally positive or negative everyday incidents, b)whether they were healthy or ill, and c)which stress system parameter was investigated. In this chapter, the Integrative Single-Case Study design is introduced as a holistic research option, presented in detail in its methodology, and critically discussed in terms of its limitations.

Breast cancer related lymphoedema: a review of contemporary preventive strategies.

Secondary lymphoedema remains an incurable long-term complication of breast cancer treatment. Prevention is our best chance against this debilitating condition. Strategies for selective de-escalation of oncological therapies have continued to evolve over the last few decades to reduce the incidence of this feared complication. In this manuscript we first review the current strategies in de-escalation of axillary treatment. We then review the current evidence for immediate lymphatic reconstruction in those high-risk patients who cannot be spared from more aggressive axillary management.

Development and validation of a predictive risk tool for VTE in women with breast cancer under chemotherapy: a cohort study in China.

The incidence of venous thromboembolism (VTE) is significantly elevated in breast cancer patients, with a three-to-fourfold increase, and further escalates to sixfold in those undergoing chemotherapy. This study aims to identify the risk factors for VTE and develop a Nomogram risk prediction model distinct from the traditional Khorana score. Univariate Cox regression analysis assessed the impact of each variable on the occurrence of VTE, while stepwise multivariate Cox regression analysis identified independent predictors. Based on these results, we constructed a Nomogram model. The model's performance was validated using the C-index, receiver-operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA). Comparisons were made with the Khorana score to evaluate the practical application value. Out of the 903 patients, 108 (11.96%) developed VTE. Cox regression analysis identified that Stage, undergoing surgery, age, white blood cells (WBC), D-dimer, and carcinoembryonic antigen (CEA) were significant risk factors for VTE (P < 0.05). The Nomogram model's C-index was 0.77 (95% CI 0.72-0.83) in the training set and 0.76 (95% CI 0.69-0.84) in the validation set. The model demonstrated excellent predictive accuracy and generalizability on the receiver-operating characteristic (ROC) curves and calibration curves. Compared to the traditional Khorana score, the Nomogram model showed superior predictive accuracy and greater clinical benefit. This study established a VTE risk prediction model for breast cancer patients undergoing chemotherapy. The model is characterized by its intuitive and straightforward application, making it highly suitable for rapid VTE risk assessment in clinical practice.

A multicenter, phase II trial of triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for highly emetogenic chemotherapy in breast cancer (PATROL-II).

Dexamethasone is an antiemetic drug widely used to prevent nausea and vomiting caused by anticancer drugs. However, dexamethasone can cause several side effects even after short-term administration. Therefore, the development of dexamethasone-free antiemetic therapies has been recognized as an important challenge. The objective of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine. Patients who were chemotherapy-naïve and scheduled to receive highly emetogenic chemotherapy for breast cancer were enrolled and assessed for nausea and vomiting occurring within 120h after the start of chemotherapy. The primary endpoint was the total control (TC) rate of overall phases. Secondary endpoints included the complete response (CR) rate, which was evaluated during the acute, delayed, and overall phases. A total of 88 patients were enrolled from eight centers in Japan, of whom 84 were included in the analysis. The proportion of patients achieving TC throughout the overall period was 17.1%. Similarly, CR and CC rates for the overall period were 43.4% and 39.5%, respectively. Frequently reported adverse events were loss of appetite and constipation, with rates of 52.4% and 50.0%, respectively. The primary endpoint was not achieved. Therefore, antiemetic therapy without dexamethasone shows an inadequate effect on nausea, and it is generally advisable to avoid omitting dexamethasone. However, in the overall period, both CR and CC were comparable to conventional three-drug combination therapy. Thus, in patients unable to use dexamethasone, replacing it with olanzapine could be an option.Trial registration number: UMIN 000038644, November 20, 2019. The date of first trial registration: 13/03/2020.

Radioiodinated Nanobody immunoPET probe for in vivo detection of CD147 in pan-cancer.

To develop the extracellular matrix metalloproteinase inducer (CD147)-targeting therapeutic strategies, accurate detection of CD147 expression in tumors is crucial. Owing to their relatively low molecular weights and high affinities, nanobodies (Nbs) may be powerful candidates for cancer diagnosis and therapy. In this study, we developed a novel CD147-targeted nanobody radiotracer, [124I]I-NB147, which provides guidance for the noninvasive detection of CD147-overexpressing cancers. CD147 expression in human cancers was detected via immunohistochemistry (IHC) on tissue microarrays (TMAs). Western blot (WB) and flow cytometry were used to screen CD147-positive malignant melanoma (MM), triple-negative breast cancer (TNBC), and pancreatic cancer (PCA) cell lines. The CD147 nanobody (NB147) was labeled with [124I]INa using Iodogen as the oxidizing agent and was purified by the PD-10 column. The physicochemical properties, affinity, metabolic characteristics, biodistribution, and immunoPET imaging of [124I]I-NB147 were evaluated Moreover, [18F]F-FDG was used as a control. Finally, CD147 expression analysis was performed via multiplex immunofluorescence (MxIF) and autoradiography on human cancer specimens and tumor-bearing mice tissues. TMAs results revealed that CD147 is highly expressed in MM, TNBC, and PCA. A CD147-specific nanobody, NB147, was successfully generated with excellent in vitro binding characteristics. [124I]I-NB147 was obtained with high radiochemical yield and purity, and was stable for at least 4h in vitro. WB and FCM revealed that CD147 was positive in A375, MDA-MB-435 and ASPC1 cells, whereas SK-MEL-28, 4T1 and BXPC3 cells presented low expression levels. The radio-ELISA results indicated that [124I]I-NB147 had a high binding affinity to CD147. The uptake of [124I]I-NB147 was significantly different between CD147 high-expression cells and CD147 low-expression cells (P < 0.001). The biological half-life of the distribution and clearance phases were 0.05h and 1.58h, respectively. In CD147-positive tumor models, the [124I]I-NB147 accumulated in A375, MDA-MB-435, and ASPC1 tumors, and the uptake value was significantly higher than that of [18F]F-FDG. Uptake in SK-MEL-28, BXPC3, and 4T1 tumors was not clearly observed. Finally, through autoradiography and histological studies, the correlation analysis between tumor uptake and CD147 expression level was determined. The high expression of CD147 in MM, TNBC, and PCA tissuesand in tumor cells was verified. The CD147 nanobody, NB147 was produced and radiolabeled to obtain the immunoPET probe, [124I]I-NB147, which showed high affinity to CD147 and precise visualization for accurate diagnosis of CD147-expressing lesions in different cancers. These results provide insight into the imaging and binding properties of nanobody NB147 over extended periods of time, reinforcing its potential in developing radionuclide therapies for CD147-positive cancer patients.