Breast Cancer Research Articles

Fear of the Cancer Coming Back: A Metasynthesis of Fear of Recurrence in Breast Cancer.

This review aimed to consolidate existing knowledge on this phenomenon by incorporating direct testimonies from individuals who have experienced breast cancer. A thorough metasynthesis of qualitative studies was conducted. English articles published prior to September 18 2023 were searched from eight databases, including PubMed, Cochrane Library, Web of Science, Embase, the Chinese biomedical literature service system, the China National Knowledge Infrastructure, the Wanfang Database, and the Wipu Database. After screening the titles, abstracts, and full texts, six articles were finally included in the quality appraisal and metaaggregation. A total of 30 research findings were distilled and integrated into three themes: causes of fear of cancer recurrence (FCR); feelings of FCR; coping with FCR; and six subthemes: disease treatment factors; psychological factors; FCR is worry and fear; overcoming; negative response; positive response. FCR is a subjective feeling; it is influenced by the interplay between the external environment (adjuvant therapy) and internal environment (psychological factors). Therefore, future care measures should be designed comprehensively, considering the individual characteristics of breast cancer survivors and the external environment. This could be the primary focus for addressing FCR in cancer patients in the future.

Breast cancer incidence and mortality, by age, stage and molecular subtypes, by race/ethnicity in Canada.

Breast cancer (BC) characteristics and outcomes in Canada related to race/ethnicity are not currently documented. Age-specific and age-standardized BC incidence and mortality rates, age distribution of cases, proportions of stage, and molecular subtypes were calculated for women aged 20+, by race/ethnicity, using 2006 and 2011 Canadian Census Health and Environment Cohort databases of linked census, cancer, and death data. In 47105 BC cases, age-specific incidence rates were higher in Filipina (rate ratio (RR) = 1.27, 95%CI, 1.11-1.46) and multiethnicity (RR = 1.57, 95% CI, 1.18-2.08) compared to White women aged 40-49; and Filipina (RR = 1.16, 95% CI, 1.02-1.31) and Arab (RR = 1.3, 95% CI, 1.02-1.65) women aged 50-59. Median age at diagnosis was 63 among White women and 52-60 among other race/ethnicity groups, with 22.4%-41.1% of cases (P < .001) diagnosed before age 50 compared to 16.6% among White women. BC was diagnosed at stage I less frequently among Filipina (38.6%), Black (39.2%), South Asian (40.6%), and First Nations (40.7%) compared to White (46.5%) and Chinese (49.6%) (P < .05) women. Black women had higher proportions of BC diagnoses at stages III and IV combined (26.3%) than White women (17.0%, P = .001). The proportion of triple-negative BC among Black women (20.5%) was higher than among White (9.5%, P < .001). Compared to White, age-specific BC mortality rates were higher among Black women aged 40-49 (RR = 1.4, 1.06-1.85) as well as First Nations (RR = 1.21, 1.01-1.45) and Métis (RR = 1.48, 1.15-1.91) women aged 60-69. Compared to White women, other Canadian women had an earlier peak age of BC diagnosis and higher proportions of cases diagnosed under age 50. Although many race/ethnicity groups had lower BC incidence and mortality than White, the higher age-specific BC mortality among Black 40-49 and First Nations and Métis women 60-69 merits further investigation.

The role of adjuvant endocrine treatment in ER+, PR−, HER2− early breast cancer: a retrospective study of real-world data

Purpose: Estrogen receptor-positive (ER+), progesterone receptor-negative (PR-) and human epidermal growth factor receptor 2-negative (HER2−) breast cancer (BC) often developed resistance to endocrine treatment (ET). We aimed to explore (1) the different clinicopathological features between ER+/PR+/HER2- and ER+/PR-/HER2- BC, and (2) whether ER+/PR-/HER2- early BC patients could benefit from adjuvant ET. Methods: All patients treated for ER+/HER2- early BC who underwent surgery between 2010 and 2021 from a BC database in China were retrospectively examined. The cases followed up for less than six months were excluded. Results: The records of ER+/PR+/HER2- (n = 10843) and ER+/PR-/HER2- BC (n = 1193) cases were reviewed, with median follow-up times of 35.8 and 47.0 months, respectively. Compared with ER+/PR+/HER2- cases, ER+/PR-/HER2- BC occurred more in postmenopausal women (73.1% vs. 52.9%, p = 0.000) and were more likely to be T > 2 cm (40.6% vs. 37.6%, p = 0.048) and Ki67 > 20%+ (48.1% vs. 36.9%, p = 0.000). However, ER+/PR-/HER2- cases had fewer nodal involvement (32.9% vs. 36.9%, p = 0.000). Approximately 82.2% (981/1193) of ER+/PR-/HER2- patients received ET, while approximately 17.8% (212/1193) did not. Compared to patients did not receive adjuvant ET, the ET group had similar disease-free survival (DFS) (HR = 1.33, 95% confidence interval (CI): 0.68–2.59, p = 0.444) and overall survival (OS) (HR = 1.17, 95%CI: 0.37–3.68, p = 0.799). 65.7% of recurrent ER+/PR-/HER2- patients experienced distant relapse (65.7% vs. 48.2% (for ER+/PR + cases), p = 0.011). By comparison, recurrent ER+/PR+/HER2- patients were more likely to experience only local relapse (31.6% vs. 14.9% (for ER+/PR- cases), p = 0.007). Conclusions: ER+/PR-/HER2- BC was a special subtype with aggressive clinicopathological features and more tend to have distant metastasis rather than nodal involvement or local relapse. ER+/PR-/HER2- early BC did not seem to benefit from adjuvant ET.

Skimmed milk intake reduces the risk of ER− breast cancer: a Mendelian randomization analysis

BackgroundIn prior observational investigations, it has been demonstrated that the consumption of milk is associated with the incidence of breast cancer (BC). Despite the existence of a two-sample Mendelian randomization (MR) that suggests a causal relationship between milk intake and breast cancer risk, the outcomes still lack a definitive conclusion. This ambiguity may be attributed to variables such as the variety of milk ingested, estrogen levels, the specific type of BC, and potential confounding factors. Therefore, our principal objective is to establish the causal association between the consumption of skimmed milk and full cream milk and the risk of different types of BC through the utilization of two-sample and two-step MR analyses.MethodsIn this study, we analyzed single nucleotide polymorphisms associated with skimmed and full-cream milk consumption in a cohort of 360,806 individuals from European populations through genome-wide association studies. We conducted a two-sample MR analysis using three different methods: inverse variance weighting (IVW) was used as the main analysis, and MR-Egger and Weighted median were used as supplementary analyses to IVW. We also performed sensitivity analysis, which included leave-one-out analysis, Cochran's Q test to detect heterogeneity, and MR-Egger intercept analysis to detect potential biases caused by pleiotropy. We used two-step MR analysis to evaluate potential mediators of associations.ResultsIn the two-sample MR analysis, IVW analysis suggests a potential inverse causal relationship between skimmed milk and BC [OR 0.34, 95% CI (0.12–1.00), P = 0.05]. Subgroup analysis revealed that skimmed milk reduces the risk of estrogen receptor-negative (ER−) breast cancer [OR 0.18, 95% CI (0.04–0.90), P = 0.04], but not estrogen receptor-positive (ER+) breast cancer [OR 0.42, 95% CI (0.15–1.22), P = 0.11]. MR Egger reached similar results, that is, skimmed milk reduces the risk of ER− breast cancer [OR 0.006, 95% CI (0.00–0.70), P = 0.04], but not BC [OR 0.16, 95% CI (0.01–4.66), P = 0.30] and ER+ breast cancer [OR 0.50, 95% CI (0.02–12.61), P = 0.65]. Additionally, we found no causal relationship between full cream milk and BC (P > 0.05). In two-step MR analysis, we found evidence for a mediating role of BMI in the relationship between skimmed milk intake and ER-breast cancer risk.ConclusionOur findings strengthen the evidence for a protective effect of skimmed milk consumption on ER-breast cancer risk. Further two-step MR analyses suggest that this protective effect may partly result from body mass index (BMI). There is no evidence that full cream milk consumption affects the risk of BC.

Preparation of transferrin-modified IR820-loaded liposomes and its effect on photodynamic therapy of breast cancer

ObjectiveTo prepare and characterize transferrin (Tf)-modified liposomes (Lipo) encapsulating the photosensitizing agent neoindocyanine green (IR820), and to investigate their effects on breast cancer 4T1 cells as well as in a breast cancer mouse model.MethodsPhotosensitive liposomes, IR820@Lipo and Tf-IR820@Lipo, were synthesized using thin film dispersion, with encapsulation efficiency assessed via UV detection. The physicochemical properties were analyzed using transmission electron microscopy (TEM) and particle size analysis. Uptake by breast cancer 4T1 cells was evaluated through confocal laser scanning microscopy and flow cytometry, while cell proliferation inhibition was measured using the CCK8 assay. Differences in intracellular fluorescence intensity were utilized to assess drug aggregation in vivo through small animal imaging techniques. The anticancer efficacy and potential side effects of the formulations were examined through pharmacodynamic studies conducted in vivo.ResultsThe mean particle sizes of IR820@Lipo and Tf-IR820@Lipo were found to be 84.30 ± 15.66 nm and 116.20 ± 14.68 nm respectively, with zeta potentials of −8.21 ± 2.06 mV for IR820@Lipo and −5.23 ± 1.19 mV for Tf-IR820@Lipo; TEM revealed that the liposomes exhibited a spheroid morphology with uniform distribution across samples; encapsulation efficiencies reached 86.38 ± 0.99% for IR820@Lipo and an impressive 93.81 ± 1.06% for Tf-IR820@Lipo; notably, Tf-IR820@Lipo significantly inhibited proliferation while promoting apoptosis of the 4T1 cells upon laser irradiation; reactive oxygen species (ROS) detection indicated enhanced fluorescence intensity within the treated cells under light exposure when utilizing both formulations; in vivo experiments demonstrated tumor accumulation of both IR820@Lipo and Tf-IR820@Lipo, indicating effective tumor targeting within a breast cancer mouse model; pharmacodynamic assessments revealed that Tf-IR820@Lipo exhibited superior inhibitory effects against breast cancer without causing liver or kidney dysfunctions in mice nor presenting significant toxic side effects overall.ConclusionGiven its high targeting capability, potent efficacy, and low toxicity profile, Tf-IR820@Lipo holds promise as a novel therapeutic agent for breast cancer treatment when combined with photodynamic therapy (PDT), potentially offering new avenues for patient management.

Breast cancer and its determinants in Ethiopia: a systematic review and meta-analysis.

Breast cancer is the leading cause of cancer morbidity and mortality among women. Still, there is a paucity of studies to know the magnitude of the problem in Ethiopia. Hence, this review was intended to pool the prevalence and identify the determinants of breast cancer in Ethiopia. A systematic review and meta-analysis was conducted. Databases like PubMed/MEDLINE, HINARI, Science Direct, and Google Scholar, as well as websites of organisationsI organizations,rewere searched between 25 February and 6 March 2023. All observational studies in Ethiopia that reported either the magnitude and/or determinants of breast cancer regardless of publication status were included. Two authors independently assessed and extracted the data. The Joanna Briggs Institute meta-analysis of statistics assessment and review instrument quality appraisal tool was used to assess the quality of the articles. Effect estimates were done by using the random-effects model. The meta-analysis results were displayed by using forest plots. Seventeen articles were reviewed with 24 435 total participants. The pooled proportion of breast cancer morbidity among patients with cancer was 20. 58% (95% CI 17.25%, 23.90%) in Ethiopia. Consuming packed foods (POR=2.12, 95% CI 1.41, 3.17), presence of high cholesterol (POR=4.08; 95% CI 2.75, 6.07), physical inactivity (POR=3.27; 95% CI 1.80, 5.94), high body mass index (BMI) (POR=2.27; 95% CI 0.85, 6.03), postmenopause (POR=2.25; 95% CI 1.63, 3.10), family history of cancer (POR=3.65; 95% CI 0.85, 15.71) and lack of breastfeeding (POR=2.76; 95% CI 0.90, 7.92) were the determinants of breast cancer. One of five patients with cancer is diagnosed with breast cancer in Ethiopia. Furthermore, more than a quarter of women with cancer suffer from breast cancer. Processed food consumption, high cholesterol in the body, lack of physical activity, high BMI, postmenopause, family history of cancer and lack of breastfeeding were the risk factors for breast cancer. The use of healthy food sources such as fruits and vegetables, and homegrown varieties of crops rather than seeking processed foods would help. CRD42023417733.

Untargeted metabolomic profiling of small extracellular vesicles reveals potential new biomarkers for triple negative breast cancer.

Breast Cancer (BC) is one of the most diagnosed malignancies among women and the second leading cause of cancer related death in North America. Triple Negative BC (TNBC), one of the most severe subtypes of BC, is extremely aggressive and has a higher chance of occurrence in women under 50 years of age. Due to a lack of regular mammographic testing in women under 50, many individuals with TNBC are diagnosed late which can decrease their survival rate. Currently, liquid biopsy is being investigated as a potentially less-invasive alternative to traditional breast tissue biopsy, but this approach is not completely reliable. Blood contains extracellular vesicles (EVs), which carry biomolecular cargo and play a role in BC progression and metastasis. Examination of small EVs could potentially yield metabolite biomarkers for early BC diagnosis. We aim to study metabolites in small EVs to find biomarkers for BC diagnosis. In this work, an untargeted nano-LC MS/MS metabolomics approach was used to analyze metabolites from small EVs derived from metastatic MDA-MB-231 and compare it with a non-cancerous MCF10A cell line. Two metabolites, LysoPC 22:6/0:0 and N-acetyl-L-Phenylalanine, unique to sEVs of MDA-MB-231, were identified, validated, and proposed as potential BC biomarkers. Metabolites from sEVs may be used for BC diagnosis.

Benefit of systemic therapy in MINDACT patients with small, ER-positive, HER2-negative breast cancers

Small, hormone receptor-positive (HR+), HER2-negative (HER2-), lymph node-negative breast cancers are associated with relatively low rates of disease recurrence and have therefore been underrepresented in clinical trials assessing the effects of systemic therapy. Consequently, it remains uncertain if this patient population derives benefit from these treatments. For this exploratory analysis, we selected MINDACT (NCT00433589) patients with a HR+, HER2-, T1ab (≤1 cm) tumor and negative lymph nodes. Patients with discordant clinical risk and MammaPrint genomic risk classification were randmomized to receive chemotherapy based on either the clinical or the genomic risk assessment. Endocrine therapy treatment was based on local guidelines. 715/6693 (10.7%) MINDACT patients had HR+, HER2-, T1abN0 breast cancer and were included in this analysis. All were clinically low-risk, 124/715 (17.3%) were genomic high-risk. For genomic high-risk tumors, 8-year distant metastasis-free survival (DMFS) was 92.9% (95% CI 86.2–96.4%) compared to 95.0% (95% CI 92.8–96.6%) for genomic low-risk tumors. For genomic high-risk tumors treated with or without chemotherapy, 8-year DMFS was 89.2% (95% CI 73.6–95.8%) and 94.1% (95% CI 82.9–98.1%), respectively. For genomic low-risk tumors, the 8-year DMFS and disease-free survival (DFS) were 96.1% (95% CI 93.4–97.6%) and 89.3% (95% CI 85.5–92.2%) when treated with endocrine therapy and 92.9% (95% CI 87.9–95.9%) and 79.4% (95% CI 72.5–84.8%) without. In conclusion, although the number of randomized patients is small, patients with small, genomic high-risk breast cancer did not seem to derive benefit from chemotherapy. Endocrine therapy was associated with improved outcomes even in genomic low-risk breast cancers.

Taxane/anthracycline combinations reduced incidence of breast cancer recurrence in young women across molecular subtypes: a real-world evidence of Taiwan from 2011 to 2019.

Adolescent and young adult (AYA) patients with breast cancer generally have poor prognoses and a higher risk of secondary cancers compared to those at the same cancer stage. Notably, AYA patients in Asia exhibit a higher incidence rate of breast cancer, with Luminal A as the predominant molecular subtype, which contrasts with the trends observed in Western countries. This study aims to compare the efficacy of Taxane/Anthracycline combination-based regimens (TACB) versus Anthracycline-based regimens (AB) in AYA patients with stage I-II breast cancer, focusing on different molecular subtypes. This study utilized data from the Taiwan National Health Insurance Research Database (NHIRD) and the Taiwan Cancer Registry (TCR) from 2011 to 2019. The study cohort included patients aged 15 to 39years who were diagnosed with stage I-II breast cancer and received either TACB or AB regimens. Propensity score matching and Cox proportional hazards regression models were used to calculate the hazard ratios (HR) for recurrence. The results showed that TACB regimens significantly reduced the risk of recurrence compared to AB regimens across all patients (aHR 0.73, 95% CI 0.55-0.97). Specifically, for low/middle-recurrence risk groups, the aHR was 0.68 (95% CI 0.49-0.96), and for high-recurrence risk groups, it was 0.43 (95% CI 0.21-0.87). The analysis further indicated no significant differences in recurrence risk between AYA and non-AYA patients using TACB regimens. The TACB regimens showed a more favorable prognosis than AB regimens across all molecular subtypes. Furthermore, TACB regimens not only outperformed AB treatments but also closed the gap in prognostic outcomes between AYA and non-AYA patients. We believe the findings of this study are highly reliable and can provide valuable guidance for physicians in choosing the most appropriate treatment strategies for AYA patients with stage I-II breast cancer.

An in silico approach uncovering the competency of oncolytic human adenovirus 52 for targeted breast cancer virotherapy

Breast cancer remains a major health threat throughout the world specifically in women above 30 years of age however, it is rarely known to affect men as well. It is characterized by the abnormal division of cells in the breast tissue resulting in the development of breast malignancies. Various risk factors contributing to breast cancer include age, family history, genetic mutations (chiefly in BRCA1 and BRCA2 genes) along with hormonal imbalances (oestrogen, progesterone, HER2). Early detection which can be obtained through frequent rounds of self-examination, mammographic scanning, and clinical assessment plays a crucial role in the prevention of the disease. In addition, appropriate diagnosis assists in better therapeutic responses. This study highlights the considerable health risks associated with the conventional treatment procedures which arise and increased demand of advanced, secure, and risk-free treatment alternatives. Oncolytic viruses are potentially apparent for the aim of improving cancer therapeutics with reduced side effects. These viruses act as the fundamental therapeutic agent themselves that selectively target and kill malignant cells without harm to healthy tissues. The key objective of the research is to provide evidence that Human Adenovirus 52 is a potent oncolytic virus and to highlight its capacity to target and eliminate cancer cells with precision while causing the least amount of harm to healthy tissues. Validating the in-silico method entails evaluating the precision and dependability of the computational modelling by contrasting the in-silico predictions with the findings from the experiments rank as the secondary objective. The workflow of this research utilized in-silico computational drug designing approaches including retrieval of tertiary structures of both the target Breast Cancer Type 1 Susceptibility Protein (BRCA1) and the viral Human Adenovirus 52 protein, their validation generating Ramachandran Plots determining favoured amino acid residue angles and prediction of their active residues. Furthermore, the study focused on the molecular dynamics docking of proteins, interpretation of molecular interactions between the docked complex, as well as the assessment of the molecular dynamic simulations (MD) in addition to their MMGBSA binding energy calculations. A successful docking between BRCA1 and Adenovirus protein provided a significant score of 329.2 +/- 24.3, furthermore, MD simulations showed a high RMSD peak at 2.8 Å, RMSF were maximum at 3.5 Å with highest protein–protein interaction, the radius of gyration was stable throughout the simulation representing elastic stability along with a high energy interaction value of - 7882 kCal/mol. Moreover, the MMGBSA calculation results showed a notable release of binding free energy of - 68.96 kCal/mol demonstrating effective bond formation between the docked complex. These findings propose the effectiveness of Human Adenovirus 52 to treat cancer. The selected oncolytic Human Adenovirus 52 is a potential candidate for the target specific treatment of breast cancer through virotherapy. This computer-aided drug discovery presents significant potential in targeting cancer cells and would assist in the development of potent drug reagents for the cancer therapy.

Impaired cyclin D3 protein degradation contributes to trastuzumab resistance in HER2 positive breast cancer

As the first anti-HER2 targeted agent approved by FDA in 1998, Trastuzumab has significantly improved the outcome of patients with HER2 positive metastatic breast cancer. Unfortunately, resistance to trastuzumab is a severe obstacle to its therapeutic efficacy in clinical application, and its mechanism has not yet been fully elucidated. In our study, we found that stabilization of cyclin D3 could be one reason for trastuzumab resistance. Trastuzumab could induce G1/G0 phase arrest by downregulating cyclin D3 protein expression. However, the protein expression of cyclin D3 was not affected in trastuzumab-resistant cells, which might be related to aberrant activation of ERK signaling pathway. Furthermore, degradation of cyclin D3 protein by trastuzumab was mainly resulted from ubiquitin-dependent proteasome mechanism instead of transcriptional regulation. In trastuzumab-resistant breast cancer cells, trastuzumab-induced degradation of cyclin D3 protein was abrogated. When the ubiquitin pathway was inhibited, cells would show a predisposition to resistance to trastuzumab. Further, CDK4/6 inhibitor can inhibit the proliferation of trastuzumab-resistant HER-2 positive breast cancer cells. Therefore, combination of CDK4/6 inhibitors and anti-HER2 targeted therapy may be an alternative and promising strategy to overcome trastuzumab resistance in the future.

Construction of a nomogram risk prediction model for depressive symptoms in elderly breast cancer patients

The primary objective of this study was to identify the factors associated with the development of depressive symptoms in elderly breast cancer (BC) patients and to construct a nomogram model for predicting these symptoms. We recruited 409 patients undergoing BC treatment in the breast departments of two tertiary-level hospitals in Jiangsu Province from November 2023 to April 2024 as our study cohort. Participants were categorized into depressed and non-depressed groups based on their clinical outcomes. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors for depression among BC patients. Multivariate analysis revealed that monthly income, pain score, family support score, and physical activity score significantly influenced the onset of depression in older BC patients (P < 0.05).The risk prediction model, constructed using these identified factors, demonstrated excellent discriminatory power, as evidenced by an area under the ROC curve (AUC) of 0.824. The maximum Youden index was 0.627, with a sensitivity of 90.60%, specificity of 72.10%, and a diagnostic threshold value of 1.501. The results of the Hosmer-Lemeshow goodness-of-fit test (χ² = 3.181, P = 0.923) indicated that the model fit the data well. The calibration curve for the model closely followed the ideal curve, suggesting a strong fit and high predictive accuracy. Our nomogram model exhibited superior predictive performance, enabling healthcare professionals to identify high-risk patients early and implement preventative measures to mitigate the development of depressive symptoms. This study is a cross-sectional study that lacks longitudinal data and has a small sample size. Future research could involve larger samples, multicenter studies, and prospective designs to build better clinical predictive models.

Screening and validating the optimal panel of housekeeping genes for 4T1 breast carcinoma and metastasis studies in mice

The 4T1 model is extensively employed in murine studies to elucidate the mechanisms underlying the carcinogenesis of triple-negative breast cancer. Molecular biology serves as a cornerstone in these investigations. However, accurate gene expression analyses necessitate data normalization employing housekeeping genes (HKGs) to avert spurious results. Here, we initially delve into the characteristics of the tumor evolution induced by 4T1 in mice, underscoring the imperative for additional tools for tumor monitoring and assessment methods for tracking the animals, thereby facilitating prospective studies employing this methodology. Subsequently, leveraging various software platforms, we assessed ten distinct HKGs (GAPDH, 18 S, ACTB, HPRT1, B2M, GUSB, PGK1, CCSER2, SYMPK, ANKRD17) not hitherto evaluated in the 4T1 breast cancer model, across tumors and diverse tissues afflicted by metastasis. Our principal findings underscore GAPDH as the optimal HKG for gene expression analyses in tumors, while HPRT1 emerged as the most stable in the liver and CCSER2 in the lung. These genes demonstrated consistent expression and minimal variation among experimental groups. Furthermore, employing these HKGs for normalization, we assessed TNF-α and VEGF expression in tissues and discerned significant disparities among groups. We posit that this constitutes the inaugural delineation of an ideal HKG for experiments utilizing the 4T1 model, particularly in vivo settings.

Microwave imaging for breast cancer screening: protocol for an open, multicentric, interventional, prospective, non-randomised clinical investigation to evaluate cancer detection capabilities of MammoWave system on an asymptomatic population across multiple European countries.

Microwave imaging presents several potential advantages including its non-ionising and harmless nature. This open, multicentric, interventional, prospective, non-randomised trial aims to validate MammoWave's artificial intelligence (AI)-based classification algorithm, leveraging microwave imaging, to achieve a sensitivity exceeding 75% and a specificity exceeding 90% in breast screening. 10 000 volunteers undergoing regular mammographic breast cancer screening will be recruited across 9 European centres and invited to participate in the clinical study, involving MammoWave testing on both breasts. MammoWave results will be checked against the reference standard, to be intended as the output of conventional breast examination path (with histological confirmation of cancer cases) with 2 years follow-up. Anonymised clinical and MammoWave's results, including microwave images, associated features and a label provided by the AI-based classification algorithm, will be collected and stored in a dedicated electronic case report form. The prospective study will involve a comparative analysis between the output of the conventional breast examination path (control intervention) and the labels provided by MammoWave's AI system (experimental intervention). These labels will categorise breasts into two groups: breast With Suspicious Finding, indicating the presence of a suspicious lesion or No Suspicious Finding, indicating the absence of a lesion or the presence of a low-suspicion lesion. This trial aims to provide evidence regarding the novel MammoWave's AI system for detecting breast cancer in asymptomatic populations during screening. This study was approved by the Research Ethics Committee of the Liguria Region (CET), Italy (CET-Liguria: 524/2023-DB id 13399), the Research Ethics Committee of Complejo Hospitalario de Toledo (CEIC), Spain (CEIC-1094), the National Ethics Committee for Clinical Research (CEIC), Portugal (CEIC-2311KC814), the Bioethical Committee of Pomeranian Medical University in Szczecin, Poland (KB-006/23/2024) and the Zurich Cantonal Ethics Commission, Switzerland (BASEC 2023-D0101). The findings of this study will be disseminated through academic and scientific conferences as well as peer-reviewed journals. NCT06291896.

K2FeO4-Enhanced Photodynamic Therapy of Breast Cancer via In Situ Synthesis of Fe2O3 and O2.

Photodynamic Therapy (PDT) offers a promising minimally invasive treatment for breast cancer, but its efficacy is limited by the hostile tumor microenvironment (TME), including hypoxia and high glutathione (GSH) levels. Although various strategies to improve oxygen concentration or reduce reactive oxygen species (ROS) resistance for enhanced PDT have been explored, they typically require intricate design and complex synthesis of multifunctional nanocarriers. Thus, this study introduces a facile K2FeO4-induced strategy to enhance PDT efficiency in breast cancer through the tumor in situ synthesis of Fe2O3 and O2. Inspired by the successful application of K2FeO4 in ecological remediation and hemostasis, K2FeO4 reacts with GSH, biological system, H2O2, and water, to generate Fe2O3 and O2. Intratumoral injection of K2FeO4 improves the TME, followed by Ce6 administration to enhance PDT through synergistic ferroptosis. This approach boosts PDT efficacy significantly by increasing ROS generation, lipid peroxidation, and inhibiting GSH and GPX4. Proteomic analysis revealed alterations in key pathways, including endocytosis and energy metabolism. This K2FeO4-PDT strategy creates a positive feedback loop by enhancing oxidative stress, providing an interesting and promising approach to PDT.

Ly6E on tumor cells impairs anti-tumor T-cell responses: a novel mechanism of tumor-induced immune exclusion

BackgroundLymphocyte antigen 6 complex, locus E (Ly6E) has been initially demonstrated to involve in T cell activity and impair viral infectivity. Recently, high expression levels of Ly6E have been reported in tumor microenvironment (TME) of various types of cancers. However, the immunoregulatory mechanism of Ly6E manipulating TME remains unknown.MethodsTCGA database and Kaplan–Meier plotter database were used to evaluate the correlation between Ly6E expression levels and cancer patient survival. After analyzing Ly6E expression levels in human breast cancer tissues and tumor cell lines, we generated Ly6E knockout (KO) and overexpression (OE) mouse cell lines. Cell proliferation ability in vitro and the ability of growth and metastasis in mouse tumor models were compared between KO/OE and wild-type tumor cells. On day 7 after tumor implantation, tumor tissues were separated for flow cytometric assay, bulk RNA sequencing and single-cell RNA sequencing (ScRNA-seq). The role of Ly6E-expressing tumor cell on macrophage was analyzed in vitro.ResultsOur result surprisingly found that high Ly6E expression levels were associated with CD8+ T cell exclusion in tumor tissues and resistance to immunotherapy. Our data showed that knockout of Ly6E in tumor cells prompts tumor regression and inhibits tumor metastases, and Ly6E-OE tumor cells vice versa. The enhanced anti-tumor effect of Ly6E knockout in tumor cells was dependent on T cell response and formed long-lasting memory. The increase in the CD8+ T-cell infiltration into the tumor islet of Ly6E-KO tumors confirmed the role of Ly6E on T cell exclusion. ScRNA-seq analysis showed that M2 macrophages are particularly abundant in the Ly6E-expressing tumor tissues, especially M2-4 macrophage cluster identified by high levels of Arg-1, indicates that Ly6E-expressing tumor cells might restrict T cell infiltration via M2 macrophages. Moreover, in vitro assay showed that cell culture media derived from Ly6E-positive tumor cells promoted macrophage migration and M2 polarization.ConclusionOur study illuminated that Ly6E-expressing tumor cells facilitated the accumulation of M2 macrophages in TME, which contributes to CD8+ T cell exclusion and provides new insights for improving efficacy of cancer immunotherapy.

Intratumoral and peritumoral radiomics for preoperative prediction of neoadjuvant chemotherapy effect in breast cancer based on 18F-FDG PET/CT

ObjectiveTo investigate the value of 18F-FDG PET/CT-based intratumoral and peritumoral radiomics in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer.Methods190 patients who met the inclusion and exclusion criteria from 2017 to 2022 were studied. Features were extracted from the PET/CT intratumoral and peritumoral regions, feature selection was performed through the correlation analysis, t-tests, and least absolute shrinkage and selection operator regression (LASSO). Four classifiers, support vector machine (SVM), k-nearest neighbor (KNN), logistic regression (LR), and naive bayes (NB) were used to build the prediction models. The receiver operating characteristic (ROC) curves were plotted to measure the predictive performance of the models. Concurrent stratified analysis was conducted to establish subtype-specific features for each molecular subtype.ResultsCompared to intratumoral features alone, intratumoral + peritumoral features achieved higher AUC values in each classifier. The SVM model constructed with intratumoral + peritumoral features achieved the highest AUC values in both the train and test set (train set: 0.95 and test set: 0.83). Subtype-specific features improve performance in predicting the efficacy of NAC (luminal group: 0.90; HER2 + group: 0.86; triple negative group: 0.92).ConclusionIntratumoral and peritumoral radiomics models based on 18F-FDG PET/CT can reliably forecast the efficacy of NAC, thereby assisting clinical decision-making.

Genetic Testing and Analysis in Breast Cancer Patients in Greece

Genetic Testing and Analysis in Breast Cancer Patients in Greece

Reduced penetrance BRCA1 and BRCA2 pathogenic variants in clinical germline genetic testing

Prior studies have suggested the existence of reduced penetrance pathogenic variants (RPPVs) in BRCA1 and BRCA2 (BRCA) which pose challenges for patient counseling and care. Here, we sought to establish RPPVs as a new category of variants. Candidate BRCA RPPVs provided by two large clinical diagnostic laboratories were compiled to identify those with the highest likelihood of being a RPPV, based on concordant interpretations. Sixteen concordant candidate BRCA RPPVs across both laboratories were systematically assessed. RPPVs included missense, splice site, and frameshift variants. Our study establishes RPPVs as a new class of variants imparting a moderately increased risk of breast cancer, which impacts risk-informed cancer prevention strategies, and provides a framework to standardize interpretation and reporting of BRCA RPPVs. Further work to define clinically meaningful risk thresholds and categories for reporting BRCA RPPVs is needed to personalize cancer risks in conjunction with other risk factors.

The Effect of Coronavirus Pandemic on the Treatment of Gynecological and Breast Cancers

Introduction: During the COVID-19 pandemic, various groups, including women with cancer, were affected as a high-risk group in terms of disease diagnosis and treatment. Despite the importance of therapeutic changes in cancers, such as breast and gynecological cancer, there is no comprehensive study in this regard that also refers to the coronavirus. The need for a deep understanding of the impact of coronavirus on the treatment plan of this group of patients caused the researcher to design and implement this study that aims to investigate the treatment challenge among cancer patients during the COVID-19 pandemic. Materials and methods: To answer the study question, a comprehensive search was carried out in databases, such as PubMed, Web of Science Core Collection, and Scopus, using keywords, including cancer, gynecologic cancer, breast cancer, treatment, delay, and modification. Full-texted, English language and original articles were included in this study. Results: In total, 27 articles were selected for the study. The findings of this study revealed that COVID-19 greatly affects the treatment of gynecology and breast cancer. These patients experience delay or modification of cancer treatment. Increased time between diagnosis and treatment, delay, change or cancellation of surgery and change in treatment plan are the most important changes in cancer treatment during the COVID-19 pandemic. Conclusion: The COVID-19 pandemic has had a significant impact on various aspects of gynecology and breast cancer care worldwide. In the current pandemic, there has been a significant delay in the diagnosis and treatment of gynecological and breast cancer, which, due to its higher morbidity and mortality, has made the condition more difficult for cancer patients and treatment teams.