Treatment Of Breast Cancer Research Articles

The Impact of Mindfulness-Based Meditation and Yoga on Stress, Body Image, Self-esteem, and Sexual Adjustment in Breast Cancer Patients Undergoing Modified Radical Mastectomy

Background Surgical interventions are commonly utilized in the treatment of breast cancer; however, they can elicit adverse effects on women’s perceptions of femininity, leading to stress, negative body image, diminished self-esteem, and challenges in sexual adjustment. Objective This study investigates the efficacy of mindfulness-based meditation and yoga in alleviating stress, enhancing self-esteem, improving body image, and facilitating sexual adjustment among women undergoing modified radical mastectomy. Methods Using a prospective (pretest, posttest, and second-month follow-up), 2-arm (1:1), randomized controlled experimental design, the study involved 39 women (intervention group = 19, control group = 20) undergoing modified radical mastectomy. The intervention group participated in face-to-face mindfulness-based meditation and yoga sessions lasting approximately 90 minutes each over an 8-week period. Results Following the intervention, significant reductions in perceived stress and the significance attributed to breasts in sexuality were observed (P < .05), accompanied by increases in self-esteem and body perception (P < .05). However, no significant differences were observed in sexual adjustment (P > .05). Conclusions Mindfulness-based meditation and yoga interventions demonstrated efficacy in mitigating perceived stress, enhancing self-esteem, and improving body perception among women undergoing modified radical mastectomy. The findings advocate for the integration of mindfulness-based stress reduction programs, particularly during the preoperative phase, to support oncological patients, particularly those with breast cancer. Implications for Practice Psychosocial aspects such as body image, self-esteem, and sexual adjustment following radical mastectomy are frequently overlooked in clinical care. This research highlights the potential benefits of incorporating mindfulness-based yoga and meditation techniques into nursing interventions to alleviate stress and enhance body confidence among women undergoing mastectomy.

Development, Validation, and Visualization of a Web-Based Nomogram to Predict the Risk of Psychological Distress in Patients Undergoing Chemotherapy After Breast Cancer Surgery

Background Psychological distress of postoperative chemotherapy patients with breast cancer is significant and has a serious impact on their quality of survival. Risk prediction models can efficiently assess patients’ psychological distress and risk factors. Objectives To investigate the factors influencing psychological distress in postoperative chemotherapy patients with breast cancer and construct a nomogram model to predict the occurrence of psychological distress in patients. Methods Two hundred forty-seven women in treatment for breast cancer who were postoperative and receiving chemotherapy were recruited. Participants completed a distress management screening measure, a numerical rating scale, the Pittsburgh Sleep Quality Index, and demographic and clinical items. Results Experiencing significant psychological distress was reported by 65.6% of participants. The psychological distress risk prediction model included 5 variables: financial problems, appearance/shape, distant metastases, the Numerical Rating Scale Pain score, and fatigue. A web calculator was designed based on the model (https://77nomogram.shinyapps.io/dynnomapp/). Conclusions This study found that financial and appearance/shape problems, distant metastases, pain scores, and fatigue were predictors of greater psychological distress in women undergoing chemotherapy after breast cancer surgery. The model constructed in this study has good predictive efficacy. Implications for practice This web-based nomogram model can help healthcare professionals quickly assess the likelihood of psychological distress in patients and screen for risk factors for psychological distress.

Orbital metastases from breast cancer: three case reports

Purpose: to describe rare cases of orbital metastases from breast cancer.Material and Methods. Three cases of Luminal A(1) and B(2) breast cancer with orbital metastases were identified and studied during the period from 01.01.2018 to 01.05.2024. Metastasis to the orbit was detected 5, 2 and 1.5 years after radical mastectomy for breast cancer. Patients received chemotherapy and radiation therapy.Results. Cases of orbital metastasis originating from breast cancer were found to have a low frequency, but may be associated with a long period between cancer diagnosis and initiation of treatment. Early detection of breast cancer and its active treatment with chemotherapy and radiation therapy are important factors in preventing orbital metastasis.Conclusion. A routine follow-up surveillance after radical treatment of breast cancer is important because there is an increase risk of developing orbital metastasis. Comprehensive strategies for treating breast cancer metastases can provide long-term disease control.

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.

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.

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.

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.

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.

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.

Role of Neoadjuvant Chemotherapy and Surgery in T1 Triple-negative Breast Cancer Treatment: a Single-center, Retrospective Cohort Study

Role of Neoadjuvant Chemotherapy and Surgery in T1 Triple-negative Breast Cancer Treatment: a Single-center, Retrospective Cohort Study

A review on lipid and polymeric nano-based 17-β-estradiol delivery systems: advances and challenges

17β-estradiol (E2) is an endogenous steroid hormone pivotal for the development of female secondary sexual characteristics and the maintenance of the female reproductive system. Its roles extend beyond these physiological functions, as E2 is employed in hormone replacement therapy to alleviate symptoms associated with menopause. Furthermore, E2 exhibits therapeutic potential in the management of osteoporosis, breast cancer, and various neurological and cardiovascular conditions, partly due to its anti-inflammatory effects via modulation of the MAPK/NFκB signaling pathway. Notwithstanding, the hydrophobic nature of E2 significantly hinders the formulation of efficacious delivery systems for its clinical deployment. Recent advances have highlighted nano-based delivery systems for E2 as a promising solution to this solubility challenge. This review critically examines contemporary nano-delivery strategies for E2, particularly emphasizing lipid and polymeric nanoparticle-based systems. These nanostructures are designed to enhance stability, biocompatibility, controlled release, and targeted delivery of E2, yet the selectivity of E2 delivery for therapeutic purposes remains an ongoing challenge. The novelty of this review lies in its focus on the advances in nano-based E2 delivery systems over the past decade, a topic not extensively covered in prior literature. We present a comprehensive analysis of the encapsulation of E2 within polymeric and lipid nanoparticles, underscoring the untapped potential of these strategies. This review identifies a significant research gap, advocating for intensified experimental investigations that could pave the way for the translation of nano-based E2 therapies from bench to bedside.

Trajectories of antidepressant use after tamoxifen initiation among young and middle-aged women with breast cancer.

Antidepressant treatment patterns may change after women with breast cancer (BC) initiate tamoxifen, potentially impacting health outcomes. We characterized trajectories of antidepressant use after initiating tamoxifen among young and middle-aged women with BC, identifying risk factors for trajectory group membership. A retrospective cohort included women 18-64years-old with BC and antidepressant treatment history who received a new tamoxifen dispensing (index date). We measured longitudinal antidepressant use post-index date as 12, monthly, proportion of days covered (PDC) measurements in a 25% random sample of IQVIA PharMetrics® Plus for Academics US claims, 2006-2022. Group-based trajectory models identified latent subgroups of antidepressant use by testing 2-6-group representations; the best model fit determined by the lowest Bayesian Information Criterion, clinical interpretability, and each subgroup comprising ≥ 5% of the cohort. Using multinomial logistic regression, baseline covariates including demographics, depression status and the CYP2D6-inhibitory strength of antidepressants were evaluated as risk factors for the trajectory of antidepressant use after tamoxifen initiation. Our sample of 851 women followed four distinct antidepressant adherence trajectories after tamoxifen initiation: 12% exhibited immediately decreasing use [mean PDC (sd) 8% (± 7)]; 7% exhibited delayed decreasing use [41% (± 14)]; 20% exhibited dynamic-moderate use [54% (± 15)]; and 60% exhibited consistently high use [91% (+ 7)]. Age, depression, and treatment with non CYP2D6-inhibiting antidepressants were associated with women's trajectory of antidepressant use after initiating tamoxifen. Nearly 40% of women were nonadherent to antidepressants after tamoxifen initiation. Future research should explore cancer-related and mental health implications of this nonadherence.

Enzyme-free and highly sensitive detection of human epidermal growth factor receptor-2 based on MNAzyme signal amplification in breast cancer.

As a common cancer biomarker, human epidermal growth factor receptor-2 (HER2) is highly expressed in breast cancer. Consequently, developing a simple and accurate HER2 sensing platform is of great significance for early diagnosis and treatment of breast cancer. Herein, we developed a rapid enzyme-free fluorescent assay biosensor based on MNAzyme signal amplification for breast cancer biomarker, HER2. The MNAzyme consists of multiple parts, including complementary DNA (cDNA) and two parts of DNAzyme (partzyme A/B). Initially, cDNA is blocked by combining with the HER2 aptamer to form a double-stranded DNA. When HER2 is present, cDNA is released as a result of the binding between HER2 and its aptamer. Due to the complementary sequences among cDNA and partzyme A/B, the MNAzyme is successfully assembled to cleave the substrate, recovering the fluorescence output. The MNAzyme biosensor exhibited a low detection limit of 0.02 ng mL-1 and excellent selectivity. Furthermore, the proposed biosensor can also change the recognition element by changing the aptamer sequence to detect various biomarkers, holding great potential for cancer diagnosis and other related biomedical applications.

Shared genetics between breast cancer and predisposing diseases identifies novel breast cancer treatment candidates.

Current effective breast cancer treatment options have severe side effects, highlighting a need for new therapies. Drug repurposing can accelerate improvements to care, as FDA-approved drugs have known safety and pharmacological profiles. Some drugs for other conditions, such as metformin, an antidiabetic, have been tested in clinical trials for repurposing for breast cancer. Here, we exploit the genetics of breast cancer and linked predisposing diseases to propose novel drug repurposing opportunities. We hypothesize that if a predisposing disease contributes to breast cancer pathology, identifying the pleiotropic genes related to the risk of cancer could prioritize drugs, among all drugs treating a predisposing disease. We aim to develop a method to not only prioritize drugs for repurposing, but also to highlight shared etiology explaining repurposing. We compile breast cancer's predisposing diseases from literature. For each predisposing disease, we use GWAS summary statistics data to identify genes in loci showing genetic correlation with breast cancer. Then, we use a network approach to link these shared genes to canonical pathways. Similarly, for all drugs treating the predisposing disease, we link their targets to pathways. In this manner, we are able to prioritize a list of drugs based on each predisposing disease, with each drug linked to a set of implicating pathways. Finally, we evaluate our recommendations against drugs currently under investigation for breast cancer. We identify 84 loci harboring mutations with positively correlated effects between breast cancer and its predisposing diseases; these contain 194 identified shared genes. Out of the 112 drugs indicated for the predisposing diseases, 74 drugs can be linked to shared genes via pathways (candidate drugs for repurposing). Fifteen out of these candidate drugs are already in advanced clinical trial phases or approved for breast cancer (OR = 9.28, p = 7.99e-03, one-sided Fisher's exact test), highlighting the ability of our approach to identify likely successful candidate drugs for repurposing. Our novel approach accelerates drug repurposing for breast cancer by leveraging shared genetics with its known predisposing diseases. The result provides 59 novel candidate drugs alongside biological insights supporting each recommendation.

Abstract B013: Investigation of a novel lncRNA, TROLL-9, in breast cancer formation and progression

Abstract Breast cancer (BC) is the most diagnosed cancer and the second leading cancer-related cause of mortality among women in the US. Despite advances in treatment, BC remains a challenge due to its metastatic potential. The most aggressive BC subtype, triple negative (TN), often harbors mutations in the tumor suppressor gene, p53. One of the effects of mutant p53 involves the inhibition of the tumor and metastatic suppressive functions of TAp63, a p53 family member. Loss of TAp63 leads to the formation of metastatic mammary adenocarcinomas in mice, in part through the regulation of a group of nine long non-coding RNAs (lncRNAs), that we identified and named TAp63 regulated oncogenic lncRNAs (TROLLs). We previously characterized two TROLLs, TROLL-2 and TROLL-3, as markers of tumor progression in multiple cancer types via the activation of the AKT pathway. Currently we are investigating the role of another member, TROLL-9. To investigate the biological role of TROLL-9, we performed in vivo experiments using preclinical mouse models. Specifically, MCF-DCIS, MCF-CA1D, and MDA-MB-231 triple negative breast cancer (TNBC) cells constitutively expressing TROLL-9 were generated and utilized for two mouse models: orthotopic xenografts for primary tumor growth and spontaneous metastasis. The former was designed to identify the potential role of TROLL-9 in tumor formation, whereas the latter involved the resection of a primary tumor and monitoring for metastases via bioluminescence imaging. Notably, TROLL-9 overexpression led to increased formation of lung and livers metastases in all these models, suggesting a role for TROLL-9 in the metastatic cascade. In order to elucidate the mechanism of function of TROLL-9, two complementary approaches were used. Firstly, pulldown using MS2-TRAP followed by mass spectrometry (MS) was performed and led to the identification of putative protein interactors. In parallel, Laser Capture Microscopy (LCM) of the lung metastases followed by RNA-sequencing was used to assess for any gene expression changes due to TROLL-9 overexpression. Integration of the two datasets is currently being performed to unveil the network of genes and proteins perturbed by TROLL-9. Furthermore, to understand the relevance in BC patients, TROLL-9 expression levels were analyzed in the TCGA BC dataset. Interestingly, differences in TROLL-9 levels across BC subtypes were observed, thus supporting its putative role in TNBC. Overall, our data suggest a role for TROLL-9 in BC progression. Our findings provide evidence for further characterizing its mechanism of function as a potential therapeutic target for the treatment of invasive BC, particularly TNBC harboring TP53 mutations. Citation Format: Avani A Deshpande, Marco Napoli, John H Lockhart, Christina L Carr, Jaden R Baldwin, Elsa R Flores. Investigation of a novel lncRNA, TROLL-9, in breast cancer formation and progression [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B013.

Performance of an AI-powered visualization software platform for precision surgery in breast cancer patients.

Surgery remains the primary treatment modality in the management of early-stage invasive breast cancer. Artificial intelligence (AI)-powered visualization platforms offer the compelling potential to aid surgeons in evaluating the tumor's location and morphology within the breast and accordingly optimize their surgical approach. We sought to validate an AI platform that employs dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to render three-dimensional (3D) representations of the tumor and 5 additional chest tissues, offering clear visualizations as well as functionalities for quantifying tumor morphology, tumor-to-landmark structure distances, excision volumes, and approximate surgical margins. This retrospective study assessed the visualization platform's performance on 100 cases with ground-truth labels vetted by 2 breast-specialized radiologists. We assessed features including automatic AI-generated clinical metrics (e.g., tumor dimensions) as well as visualization tools including convex hulls at desired margins around the tumor to help visualize lumpectomy volume. The statistical performance of the platform's automated features was robust and within the range of inter-radiologist variability. These detailed 3D tumor and surrounding multi-tissue depictions offer both qualitative and quantitative comprehension of cancer topology and may aid in formulating an optimal surgical approach for breast cancer treatment. We further establish the framework for broader data integration into the platform to enhance precision cancer care.

Production, Characterization, and Application of Hydrophobin-Based IR780 Nanoparticles for Targeted Photothermal Cancer Therapy and Advanced Near-Infrared Imaging.

As a promising approach for breast cancer treatment, photothermal therapy (PTT) features high spatial selectivity, noninvasiveness, and minimal drug resistance. IR780 (a near-infrared fluorescent dye) serves as an effective photosensitizer in PTT cancer therapy. However, the clinical application of IR780 in PTT has been hindered by its poor water solubility and unstable photostability. In this study, a genetically engineered dual-functional fusion protein tLyP-1-MGF6 is successfully constructed and expressed, which presents a novel use of hydrophobin MGF6 for its amphiphilicity combined with the tumor-penetrating peptide tLyP-1 to create an innovative carrier for IR780. These results show this fusion protein serving as a biodegradable and biocompatible carrier, significantly improves the water solubility of IR780 when formulated into nanoparticles. These studies demonstrate that the IR780@tLyP-1-MGF6 nanoparticles significantly enhance tumor targeting and photothermal therapeutic efficacy in comparison with control in vitro and in vivo. These advancements highlight the potential of the unique combination hydrophobin-based IR780 delivery system as a multifunctional nanoplatform for integrated imaging and targeted photothermal treatment of breast cancer.

FXR deficiency induced ferroptosis via modulation of the CBP-dependent p53 acetylation to suppress breast cancer growth and metastasis.

Farnesoid X receptor (NR1H4/FXR) functions as a scavenger of lipid peroxide products and drives the proliferation and metastasis of various cancers. However, the underlying molecular mechanisms remain poorly understood. In our study, we found that the expression levels of FXR, vimentin and SLC7A11 were significantly higher in breast cancer tissues, particularly in metastatic cancer tissues compared to non-metastatic ones. Furthermore, the increased FXR expression was positively correlated with vimentin and SLC7A11 in clinical tumor specimens. In addition, a high level of FXR correlated with poor prognosis in patients with breast cancer. Both Z-Guggulsterone (Z-GS), as a pharmacological inhibitor of FXR, and silencing FXR curbed proliferation and migration of breast cancer cells by promoting ferroptosis. Notably, our results showed that FXR competitively bound to CREB-binding protein (CBP) to suppress the interaction between p53 and CBP in the nucleus, and thus prevented p53 acetylation at lys382, which was essential for upregulating the expression of SLC7A11. Conversely, FXR knockdown increased the interaction between p53 and CBP and promoted p53 acetylation, which ultimately led to facilitating ferroptosis in breast cancer cells. More importantly, we also found that Z-GS inhibited TGF-β1-induced tumor growth and metastasis of breast cancer primarily through ferroptosis via regulating CBP-dependent p53 acetylation in nude mice. In conclusion, the FXR was first reported as a tumor promoter that enhanced the proliferation and metastasis of breast cancer cells through regulating CBP-dependent p53 K382 acetylation. It proposes that FXR may serve as a potential therapeutic target for the treatment of breast cancer.

Injectable Polydopamine Nanoparticle-Incorporated Hydrogels for Antiangiogenesis and Stimulating Tumoricidal Immunity to Inhibit Metastasis and Recurrence Postresection.

Surgical resection is still the main means for clinical treatments of breast cancer, but the postoperative immunosuppressive microenvironment and neoangiogenesis of the residual tumors easily lead to tumor metastasis and recurrence, which will further endanger patients' lives. The combination of antiangiogenic therapy and immunotherapy may promote the mutually reinforced cycle of immune reprogramming and vascular normalization to avoid tumor metastasis and recurrence. Herein, we prepared polydopamine nanoparticles for improving tissue adhesion and enriching tumor-associated antigens. This nanoregulator together with regorafenib (REG) was further incorporated into a hydrogel developed from grafting adipic acid dihydrazide onto 2,2,6,6-tetramethylpiperidine-1-oxyl radical oxidized chitin and oxidized hyaluronic acid, which was injectable at the cavity after subcutaneous tumor surgery with good mechanical properties and degradability. The system showed long-term release of REG. After combining with anti-PD-L1, the hydrogel applied to the surgical wound exhibited a reduction in tumor metastasis and recurrence. This effect was achieved by suppressing angiogenesis and enhancing antitumor immunity, characterized by increased levels of effector T lymphocytes and activation of dendritic cells within tumors, spleens, and draining lymph nodes. The injectable hydrogel offers a promising strategy for postoperative management aimed at preventing tumor metastasis and recurrence.

Breast cancer and ATM mutations: treatment implications.

Genetic testing for breast cancer predisposing genes has expanded beyond BRCA1 and BRCA2 and now includes panels of 20 or more genes. It is now recommended that all women diagnosed with breast cancer at age 65 or below be offered testing for an extended gene panel. The rationale for testing includes personalizing the management of breast cancer according to the mutation found. For BRCA1 and BRCA2 carriers, the finding of a mutation has clear implications for cancer management, but for other genes, such as ATM, the management implications are less clear. Women with an ATM mutation have a lifetime risk of breast cancer of approximately 25%, the majority of which are ER-positive. The risk of ovarian cancer is approximately 5%. It is not yet clear how the identification of an ATM mutation in a patient newly diagnosed with breast cancer should impact on her treatment and follow-up. At present, these women are treated in the same way as women without a mutation. It is important that large prospective studies be conducted looking at various treatment modalities in women with breast cancer and an ATM mutation in order to optimize outcomes.