Breast Cancer Research Articles

Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk factors

Abstract Background Assessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive history, and genotyping of major mutations. However, assessing the impact of environmental factors, such as lifestyle, health-related behavior, or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic and environmental effects, presents a promising opportunity. Previous studies have identified associations and predicted the risk of BC using DNAm in blood; however, these studies did not distinguish between genetic and environmental contributions to these DNAm sites. In this study, associations between DNAm and BC are assessed using paired twin models, which control for shared genetic and environmental effects, allowing testing for associations between DNAm and non-shared environmental exposures and behavior. Results Pre-diagnosis blood samples of 32 monozygotic (MZ) and 76 dizygotic (DZ) female twin pairs discordant for BC were collected at the mean age of 56.0 years, with the mean age at diagnosis 66.8 years and censoring 75.2 years. We identified 212 CpGs (p < 6.4*10–8) and 15 DMRs associated with BC risk across all pairs using paired Cox proportional hazard models. All but one of the BC risks associated with CpGs were hypomethylated, and 198/212 CpGs had their DNAm associated with BC risk independent of genetic effects. According to previous literature, at least five of the top CpGs were related to estrogen signaling. Following a comprehensive two-sample Mendelian randomization analysis, we found evidence supporting a dual causal impact of DNAm at cg20145695 (gene body of NXN, rs480351) with increased risk for estrogen receptor positive BC and decreased risk for estrogen receptor negative BC. Conclusion While causal effects of DNAm on BC risk are rare, most of the identified CpGs associated with the risk of BC appear to be independent of genetic effects. This suggests that DNAm could serve as a valuable biomarker for environmental risk factors for BC, and may offer potential benefits as a complementary tool to current risk assessment procedures.

Importance of LINC00852/miR-145-5p in breast cancer: a bioinformatics and experimental study

Abstract Purpose We aimed to examine the importance of an lncRNA, namely LINC00852, in the pathogenesis of breast cancer. Materials and methods In the current study, we used several online tools to examine the importance of LINC00852 in breast cancer. Then, we examined these findings in 50 pairs of breast cancer tissues and adjacent non-cancerous ones. We also re-evaluated the data of miR-145-5p signature from our recent study. Results While in silico tools revealed down-regulation of LINC00852 in breast cancer samples, expression assays showed significant up-regulation of this lncRNAs in breast cancer samples compared with matching control samples from Iranian patients. miR-145-5p was under-expressed in breast cancer samples compared with non-cancerous samples. LINC00852 could separate breast cancer tissues from adjacent non-malignant tissues with an AUC value of 0.7218 (P value < 0.001). Conclusion The current study potentiates LINC00852/miR-145-5p axis as a possible contributor to the pathogenesis of breast cancer.

Group medical visits in cancer survivorship care: a scoping review

Abstract Background More than 60% of cancer survivors report unmet physical, psychosocial, and informational needs. The care of cancer survivors includes surveillance, health maintenance monitoring, referral for long-term adverse effects of cancer treatment, and coordination of care. Group medical visits (GMV) include medical care, education, and peer support and can be used to facilitate the delivery of multidisciplinary survivorship care. We aimed to characterize the current state of related research describing the role of GMV in cancer survivorship care. Methods For this scoping review, we searched for published literature using PubMed, Embase, and other resources. We included intervention studies of multidisciplinary care involving GMVs of adult patients with a history of cancer requiring the presence of medical personnel, physicians, advanced practitioners, or oncology nurses. We included studies that focused on broad cancer survivorship care, rather than those using specific modalities, such as yoga, or limited to specific aspects of cancer survivorship care, such as weight loss. We characterized the studies by cancer type, structure of GMVs, and reported outcomes. Results We identified 2311 studies (2122 from PubMed and 189 from Embase). We excluded 1524 duplicates and screened 787 studies for title and abstract review. Finally, 63 studies were retrieved for full-text review, and six were included in this scoping review. Of the included studies, four were non-randomized, and two were randomized. Breast cancer was the most common site (4); other studies included breast and other cancers (1) and hematopoietic transplant cancer survivors (1). There was heterogeneity in the structure and frequency of sessions and the survivorship domains addressed. The outcomes studied included quality of life, healthcare utilization, and costs. Conclusions Limited high-quality research exists on the role of GMV in cancer survivorship. Though shown to be effective in chronic disease, the evidence for the effectiveness of this important and widely used approach in multidisciplinary survivorship care remains inconsistent and preliminary; the literature to date provides a starting point for larger-scale studies of GMV in cancer survivorship care. Implications for Cancer Survivors While Group medical visits are a promising intervention to provide multidisciplinary care, larger studies are needed to support their benefit in the care of cancer survivors.

Impact of a Physical Exercise and Health Education Program on Metabolic Syndrome and Quality of Life in Postmenopausal Breast Cancer Women Undergoing Adjuvant Treatment with Aromatase Inhibitors

Background and Objectives: Adjuvant treatment with aromatase inhibitors (AIs) in breast cancer (BC) survivors can cause adverse effects such as metabolic syndrome (MS) (insulin resistance, central obesity, atherogenic dyslipidemia, and hypertension) associated with morbidity and premature mortality. We evaluate the effect of a multimodal program based on physical exercise and health education on MS and health-related quality of life (QoL) in postmenopausal women with BC under AIs. Methods: A total of 56 postmenopausal women, diagnosed with BC, aged 60 years or older (mean age 67.2 years) and on hormonal treatment with AIs, were included in the multimodal physical exercise and health education program, and evaluated before and after their participation. The assessment of the five criteria of the MS included the following: waist circumference, high blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Two main instruments were used to evaluate the impact of the intervention on QoL: the EORTC QLQ C30 (questionnaire for cancers in general) and the EORTC QLQ BR23 (specifically for breast cancer patients). The EuroQol 5D (EQ-5D) was also used to compare these results. Results: The percentage of women meeting the MS criteria was 37.7% at baseline and fell to 15.1% at 3 months after the intervention (p = 0.02). The intervention significantly reduced hypertension (p < 0.001), central obesity (p < 0.001), and the concentration of triglycerides (p = 0.016). No significant changes were observed in fasting glucose and HDL concentration. A statistically significant improvement was found in QoL (on both the QLQ30 and BR23 scales). A multivariate regression model analysis identified marital status (being married) (95% CI: 1.728–131.615, p = 0.014), and percentage of attendance at health education sessions (95% CI: 1.010–1.211, p = 0.029) as positive predictive variables of improvement in MS. Conclusions: The implementation of multimodal, community-based programs of physical exercise and health education improve the prevalence of MS and specific criteria of MS and QoL in postmenopausal women with breast cancer receiving AI treatment.

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.

New insights into the role of the CHI3L2 protein in invasive ductal breast carcinoma

AbstractChitinase-like proteins have multiple biological functions that promote tumor growth, angiogenesis and metastasis. Expression of CHI3L2, which is similar in structure to CHI3L1, is detected in glioma cells and tumor-associated macrophages (TAMs) in glioma and breast cancer. However, its exact role remains unclear. We analyzed the expression of CHI3L2 in 74 invasive ductal breast carcinoma (IDC) tumors, breast cancer and macrophages cell cultures using immunohistochemistry, immunofluorescence, Western blot and PCR methods. Clinicopathologic data were included in the analysis. The results obtained show that CHI3L2 expression decreases with increasing degree of tumor grade and negative status of estrogen (ER) and progesterone receptors (PR). Furthermore, CHI3L2 is significantly and positively correlated with phosphorylation of STAT-3 and ERK1/2 signaling pathways, but negatively correlated with macrophage infiltration. CHI3L2 is expressed both in the cytoplasm of cancer cells and in macrophages and may regulate STAT-3 and ERK1/2 phosphorylation in breast cancer cell lines. Analysis of the clinicopathologic data revealed that CHI3L2 levels had no effect on patient survival. CHI3L2 expression may be specific for cancer cells in IDC and involved in cross-talk with the tumor microenvironment. Our study has shown that IDC cancer cells express the CHI3L2 protein, possibly indicating a novel function of this protein.

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.

Pretreatment plasma vitamin D and response to neoadjuvant chemotherapy in breast cancer: evidence from pooled analysis of cohort studies

Background: Biological evidence has revealed anti-tumor effect of vitamin D, but whether it could predict the response to neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients remains inconclusive. The aim was to investigate the association between pretreatment vitamin D level and response to NAC and subsequent survival outcomes in BC patients. Materials and Methods: We systematically searched the Medline, Embase, Cochrane Library and Web of Science databases and clinical trial registries to identify relevant articles from inception to October 8, 2024. Eligible studies investigating the associations between pretreatment plasma vitamin D and response to NAC in BC patients were selected according to the predefined criteria, with the study characteristics extracted by two reviewers. The primary outcome was pathological complete response (pCR), while overall pathological response and event-free survival (EFS) were adopted as secondary outcomes. Summary effect estimates of odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup and sensitivity analyses were performed based on study characteristics and methodological quality. Results: Six retrospective cohort studies involving 1,291 BC patients were included. We observed a significant association between pretreatment vitamin D deficiency and 50% increased odds of non-pCR after NAC (OR=1.50, 95%CI 1.11-2.03, P=0.008) with no heterogeneity (I2=0%). We also identified a significant association of vitamin D with overall pathological response (OR=1.33, 95%CI 1.01-1.75, P=0.046). A similar association with EFS (HR=1.27, 95%CI 0.92-1.75, P=0.139) was also noted although the effect estimate was not statistically significant. Sensitivity analyses based on methodological quality showed consistent findings. Conclusion: Pretreatment vitamin D deficiency is associated with an inferior response to NAC in BC patients. Our meta-analysis advocates further prospective studies with large sample sizes before vitamin D supplementation could be administered to improve NAC response and subsequent prognosis of BC patients.

The use of adjuvant chemotherapy in cats with mammary carcinomas undergoing surgical removal.

PICO Question In cats with mammary carcinomas undergoing surgical removal, does the addition of adjuvant chemotherapy compared with surgical removal alone result in increased survival time? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Five retrospective cohort studies were critically reviewed. Strength of evidence Weak. Outcomes reported In cats with mammary carcinomas undergoing surgical removal, the addition of adjuvant chemotherapy compared with surgical removal alone was significantly associated with an increase in disease-specific survival time in one of the studies. This statistical significance was not found in the other four papers. Conclusion All five studies reviewed presented weak evidence for the clinical question due to their retrospective nature and weak study design. It is, therefore, concluded that there is not enough evidence to suggest that cats with mammary carcinomas that have undergone surgical treatment will have a longer survival time if treated with adjuvant chemotherapy. More prospective, placebo-controlled, double-blinded studies are needed to understand the clinical significance of adjuvant chemotherapy in cats with mammary carcinomas.

Survivorship care plans and adherence to breast and cervical cancer screening guidelines among cancer survivors in a national sample

Abstract Purpose The impact of the components of survivorship care plans on adherence to cancer screening guidelines among cancer survivors is limited. We examined the association of receipt of treatment summaries, follow-up instructions, and type of doctor providing survivorship care with adherence to breast cancer screening (BCS) and cervical cancer screening (CCS) guidelines in female cancer survivors. Methods A cross-sectional analysis using Behavioral Risk Factor Surveillance System (BRFSS) data from 2014, 2016 and 2018 was conducted. BCS and CCS-eligible women were aged 40–74 and 30–64, respectively. BCS adherence was defined as a mammogram within 2 years and CCS adherence as a pap smear within 3 years or HPV test within 5 years. Univariate analysis with chi-square and multivariable logistic regression are reported. Results 5,001 BCS and 3,014 CCS-eligible survivors were identified. In the BCS group, recipients of treatment summaries and follow-up instructions were significantly more adherent with BCS (84.1% vs. 77.4%; 83.4% vs. 74%, respectively, p < 0.001). In the CCS group, recipients of follow-up instructions were significantly more adherent with CCS (78.1% vs. 67.7%, p < 0.001). In both groups, there was no significant difference in BCS or CCS based on type of physician providing care (p = 0.087). On multivariate analysis, receipt of follow-up instructions was the only factor significantly associated with BCS (OR:2.81; 95%CI:1.76–4.49) and CCS (OR:3.14; 95%CI:1.88–5.23). Conclusions Follow-up instructions, as part of survivorship care plans, have the strongest association with BCS and CCS among female cancer survivors. Additional research should focus on improving the distribution of survivorship care plans, particularly follow-up instructions, as a method to increase BCS and CCS among cancer survivors.

Elevated expression of APOO as a potential prognostic marker in breast cancer: insights from bioinformatic analysis and experimental validation

Elevated expression of APOO as a potential prognostic marker in breast cancer: insights from bioinformatic analysis and experimental validation

Nanoengineering of Phosphate/Phosphonate Drugs via Competitive Replacement with Metal‐Phenolic Networks to Overcome Breast Tumor with Lung and Bone Metastasis

AbstractPhosphate and phosphonate drugs are vital in building organisms, regulating physiological processes, and exhibiting diverse biological activities, including antiviral, antibacterial, antineoplastic, and enzyme‐inhibitory effects. However, their therapeutic potential is limited by the lack of advanced nanoengineering technologies. Herein, a competitive coordination strategy for nanoengineering phosphate/phosphonate drugs is introduced. By leveraging the difference in coordination capabilities between polyphenols and phosphates/phosphonates with metal ions, various phosphate/phosphonate‐based nanodrugs using metal‐phenolic networks (MPNs) as templates and phosphate/phosphonate drugs as competitive agents are constructed. The dynamic nature of these coordination bonds imparts stimuli‐responsiveness to the nanodrugs, allowing for targeted release and therapy. As a proof of concept, Fe3+ and galangin are used to form the MPN template, zoledronic acid and cGAMP as competitive agents, and DOX as the loaded drug to construct DOX@Fe‐galangin@Fe‐zoledronic acid‐cGAMP nanodrugs. The results demonstrate that, by triggering pyroptosis and activating the cGAS‐STING pathway, the nanodrugs exhibit potent cytotoxicity and accurate selectivity in eradicating orthotopic breast tumors, and activate an antitumor immune response against lung and bone metastases. Because the competitive coordination strategy is applicable to a variety of phosphate/phosphonate agents, it holds significant potential for enhancing the clinical efficacy of phosphate/phosphonate drugs and advancing nanodrug development for complex therapeutic applications.

Percutaneous cryoablation in soft tissue tumor management: an educational review

Abstract Background Percutaneous cryoablation (PCA), having shown effectiveness in treating liver, lung, prostate, breast, and kidney tumors, is now gaining attention for the treatment of soft tissue tumors. PCA functions by freezing tissue, which induces ice crystal formation and cell death without damaging collagen structures. Technical considerations include the selection and handling of cryoprobes and cryogenic agents, procedural duration, and choice of image guidance for precision. This review aims to synthesize the mechanisms, applications, and technical aspects of PCA in the treatment of soft tissue tumors. Methods Adhering to PRISMA 2020 guidelines, a review was conducted of studies published prior to March 2024 that investigated PCA of soft tissue tumors. The review focused on technical and procedural aspects of cryoablation, cryobiological principles, cellular and tissue responses to extreme cold, intra- and post-procedure physiological mechanisms during and post-procedure, and main clinical applications. Results PCA is efficient in treating soft tissue tumors, including desmoid tumors, vascular malformations, and abdominal wall endometriosis. Several cryobiological mechanisms are involved, notably ice crystal formation, cellular dehydration, osmotic effects, and the inflammatory response, all of which contribute to its efficacy. Key technical aspects include the choice of cryoprobes, cryogenic agents (argon gas or liquid nitrogen), and the duration and control of freezing/thawing cycles. PCA also frequently outperformed traditional treatments like surgery and radiotherapy in terms of pain reduction, tumor size reduction, and patient outcomes. Moreover, its nerve sideration properties make it effective under local anesthesia. Conclusion Demonstrating substantial pain reduction, tumor size decrease, and high technical success rates, PCA offers a promising and minimally invasive alternative for soft tissue tumor treatment. Critical relevance statement Percutaneous cryoablation provides a minimally invasive, precise alternative for soft tissue tumor management, advancing clinical radiology by offering effective treatment with reduced patient risk and enhanced outcomes through image-guided procedures. Key Points Percutaneous cryoablation (PCA) offers a promising, minimally invasive alternative for managing soft tissue tumors. PCA employs image-guided techniques to accurately target and treat tumors, ensuring high precision and control. PCA preserves structures like collagen, reduces pain, decreases tumor size, and generally enhances patient outcomes. Graphical Abstract

Understanding tumour growth variability in breast cancer xenograft models identifies PARP inhibition resistance biomarkers

Understanding tumour growth variability in breast cancer xenograft models identifies PARP inhibition resistance biomarkers

Down-regulation of ESRP2 inhibits breast cancer cell proliferation via inhibiting cyclinD1

Down-regulation of ESRP2 inhibits breast cancer cell proliferation via inhibiting cyclinD1

Pregnancy-Associated Breast Cancer: Key Concepts for Optimizing Diagnosis and Treatment

Pregnancy-Associated Breast Cancer: Key Concepts for Optimizing Diagnosis and Treatment

Multi-classification of breast cancer pathology images based on a two-stage hybrid network

Multi-classification of breast cancer pathology images based on a two-stage hybrid network

CAPRIN1 Transcriptionally Activated PLPP4 to Inhibit DOX Sensitivity and Promote Breast Cancer Progression

CAPRIN1 Transcriptionally Activated PLPP4 to Inhibit DOX Sensitivity and Promote Breast Cancer Progression

Effects of resistance training vs high intensity interval training on body composition, muscle strength, cardiorespiratory fitness, and quality of life in survivors of breast cancer: a randomized trial

Effects of resistance training vs high intensity interval training on body composition, muscle strength, cardiorespiratory fitness, and quality of life in survivors of breast cancer: a randomized trial

First-in-human trial using mixed-reality visualization for patient setup during breast or chest wall radiotherapy

Abstract Background The purpose of this study is to assess the feasibility of mixed-reality (MixR) visualization for patient setup in breast and chest wall radiotherapy (RT) by performing a first-in-human clinical trial comparing MixR with a 3-point alignment. Methods IRB approval was granted for a study incorporating MixR during the setup process for patients undergoing proton (n = 10) or photon (n = 8) RT to the breast or chest wall. For each patient, MixR was utilized for five fractions and compared against another five fractions using 3-point alignment. During fractions with MixR, the patient was aligned by at least one therapist wearing a HoloLens 2 device who was able to guide the process by simultaneously and directly viewing the patient and a hologram of the patient’s surface derived from their simulation CT scan. Alignment accuracy was quantified with cone-beam CT (CBCT) for photon treatments and CBCT plus kV/kV imaging for proton treatments. Registration time was tracked throughout the setup process as well as the amount of image guidance (IGRT) utilized for final alignment. Results In the proton cohort, the mean 3D shift was 0.96 cm using 3-point alignment and 1.18 cm using MixR. An equivalence test indicated that the difference in registration accuracy between the two techniques was less than 0.5 cm. In the photon cohort, the mean 3D shift was 1.18 cm using 3-point alignment and 1.00 cm using MixR. An equivalence test indicated that the difference in registration accuracy was less than 0.3 cm. Minor differences were seen in registration time and the amount of IGRT utilization. Conclusions MixR for patient setup for breast cancer RT is possible at the level of accuracy and efficiency provided by a 3-point alignment. Further developments in marker tracking, feedback, and a better understanding of the perceptual challenges of MixR are needed to achieve a similar level of accuracy as provided by modern surface-guided radiotherapy (SGRT) systems. Trial registration ClinicalTrials.gov, UFHPTI 2015-BR05: Improving Breast Radiotherapy Setup and Delivery Using Mixed-Reality Visualization, NCT05178927.