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Background: In addition to the great challenge of early diagnosis and prognosis in breast cancer (BC), the role of gene promoters in BC remains largely unexplored. This study aimed to evaluate aldo-keto reductase family 1 member B1 (AKR1B1) methylation as noninvasive biomarker for early BC diagnosis. Methods: A total of 200 (120 with BC, 40 with benign breast diseases, 40 healthy) Egyptian women were enrolled. AKR1B1 methylation level was determined using EpiTect Methyl II QPCR assay quantitative polymerase chain reaction. Results: Findings revealed that hypermethylation AKR1B1 was reported to be associated (P <.0001) with BC cases (93.2 [75.4-98.6]) compared with benign (23.9 [22.6-48.3]) or healthy (15.5 [10.6-16]) controls. It had a great diagnostic power (area under the curve [AUC] = 0.909) that was superior to cancer antigen (CA) 15-3 (AUC = 0.681) and carcinoembryonic antigen (CEA) (AUC = 0.539). Interestingly, AKR1B1 hypermethylation was reported to be significant in identifying BC early stages (AUC = 0.899) and grades (AUC = 0.903). Independent to hormonal status and HER2neu expression, AKR1B1 hypermethylation was related to some tumor severity features, including advanced stages, high histological grades, and lymph node invasion. Also, AKR1B1 high degrees of methylation were significantly correlated with the increase in CEA (r =.195; P =.027), CA-15.3 (r =.351; P =.0001) and tumor stages (r =.274; P =.014), grades (r =.253; P =.024), and lymph node invasion (r =.275; P =.014). Conclusions: This study revealed that aberrant AKR1B1 methylation could facilitate early BC detection from benign br0east disorders. Hypermethylated AKR1B1 was related to BC aggressiveness suggesting its potential role as diagnostic and prognostic BC biomarker. [ABSTRACT FROM AUTHOR]

Recurrent breast cancers often develop resistance to standard-of-care therapies. Identifying targetable factors contributing to cancer recurrence remains the rate-limiting step in improving long-term outcomes. In this study, we identify tumor cell-derived osteopontin as an autocrine and paracrine driver of tumor recurrence. Osteopontin promotes tumor cell proliferation, recruits macrophages, and synergizes with IL-4 to further polarize them into a pro-tumorigenic state. Macrophage depletion and osteopontin inhibition decrease recurrent tumor growth. Furthermore, targeting osteopontin in primary tumor-bearing female mice prevents metastasis, permits T cell infiltration and activation, and improves anti-PD-1 immunotherapy response. Clinically, osteopontin expression is higher in recurrent metastatic tumors versus female patient-matched primary breast tumors. Osteopontin positively correlates with macrophage infiltration, increases with higher tumor grade, and its elevated pathway activity is associated with poor prognosis and long-term recurrence. Our findings suggest clinical implications and an alternative therapeutic strategy based on osteopontin's multiaxial role in breast cancer progression and recurrence. Osteopontin promotes tumor growth in several cancer types. Here, in a preclinical model recapitulating features of human breast cancer recurrence, the authors report that osteopontin promotes the recruitment of immunosuppressive macrophages and its targeting reduces breast tumor growth and metastasis. [ABSTRACT FROM AUTHOR]

Introduction/objectives: The precise location of the tumor site is essential for the success of surgical treatment. Neoadjuvant chemotherapy (NAC) is a challenge for preoperative tumor and node localization. Thus, the knowledge and attitudes of the affiliated members of the Brazilian Society of Mastology (SBM) regarding breast and axilla marking were evaluated and a consensus regarding management and treatment was reached. Methods: This was an online survey conducted between June and December 2022. All 1,742 active mastologists affiliated to the SBM were invited anonymously. The online form contained 28 objective questions, of which 22 were formulated on a Likert scale. These questions addressed relevant aspects related to breast and axilla marking in the neoadjuvant setting. Responses that reached 70% agreement were considered consensual. Statistical analysis was performed using the SPSS program version 26.0. Post hoc analysis was performed when appropriate and the significance level was set at p < 0.05. Polychoric regression analyses were conducted using 'VGAM' package Results: In total, 468 mastologists answered the questionnaire (26.8%), with a predominance of professionals aged between 40-49 years (32.1%). Most professionals were board-certified (84,8%). The indication of tumor marking in the breast prior to NAC was consensual (96.4%) and the metal clip was the preferred method (69.7%). There was no consensus regarding the indication of pre-NAC histologically positive lymph node marking (49.8% disagree and 42.8% agree). However, there was consensus that the clinical and imaging evaluation was insufficient for staging the axilla as N1 (71.6%). The contraindication of breast and node marking in T4b tumors (71.2%) was consensual. There was consensus on the indication of sentinel lymph node biopsy (SLNB) for initially cN1 (92.3%) or cN2 (72.7%) tumors that became cN0 after NAC, with 67.5% opting for dual staining with technetium and patent blue. When <3 lymph nodes were retrieved 41.0% of mastologists performed axillary lymphadenectomy. Among the 28 questions, consensus was reached on only 11 (39.3%). Conclusion: The indication of pre-NAC breast marking is consensual among Brazilian mastologists, although axillary nodal marking is not. There is a great divergence of attitudes among Brazilian surgeons in relation to the many issues related to pre-NAC breast and axilla marking. [ABSTRACT FROM AUTHOR]

Background: This pilot prospective study aimed to evaluate ultrasound-guided cryoablation of breast cancer (BC) by assessing: (i) technical efficacy as the presence of necrosis in surgical specimens and rate of complete tumor ablation; (ii) safety as incidence and severity of complications; and (iii) patients' satisfaction using a dedicated questionnaire. In addition, (iv) we tested the capability of magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM) to predict cryoablation efficacy. Methods: From 07/2022 to 01/2023, we enrolled 20 patients with early-stage BC scheduled for breast surgery. Ten of them, with a cryo-feasible cancer location, were sent to cryoablation (cryo-group) and ten to routine surgical practice (control group). Both groups underwent surgery and were asked to answer a satisfaction questionnaire. Results: Of eleven patients screened for cryoablation, only one refused to be treated at another hospital (acceptance rate 10/11, 91%). Surgery was quadrantectomy in 19 cases and mastectomy in 1. In the cryo-group, the procedure was completed and steatonecrosis was observed in 10/10 cases, with complete tumor ablation in nine of them. The post-procedural status was evaluated with MRI in five patients, with CEM in four patients, and with ultrasound in one patient who refused MRI and CEM. MRI or CEM correctly predicted complete cryoablation in eight patients and incomplete cryoablation in one patient. Patients in both groups did not have serious complications and responded positively to satisfaction questionnaires. Conclusion: Ultrasound-guided cryoablation of early-stage BC is well accepted by patients, effective, and safe. MRI and CEM were able to predict the procedure's technical efficacy. Trial registration: https://clinicaltrials.gov/study/NCT05727813 updated February 14, 2023. Relevance statement: Our pilot study showed that ultrasound-guided cryoablation is a promising nonsurgical alternative for treating early-stage BC. Key Points: Ultrasound-guided cryoablation was effective and safe in early BC patients. The procedure was well-tolerated, with low morbidity and high patient satisfaction. MRI and CEM predicted cryoablation efficacy, in accordance with histopathologic findings. Cryoablation can be considered a potential alternative to surgery in selected patients. [ABSTRACT FROM AUTHOR]

Breast cancer commonly metastasises to the skeleton, and stereotactic ablative body radiation therapy (SABR) is an emerging treatment for oligometastatic disease. Accurately imaging bone metastases and their response to treatment is challenging. [18F]NaF-PET has a higher sensitivity and specificity than conventional bone scans for detecting breast cancer bone metastases. In this pre-defined secondary analysis of a prospective trial, we evaluated the change in [18F]NaF uptake after SABR. Patients with oligometastatic breast cancer received a single fraction of 20 Gy to up to three bone metastases. [18F]NaF-PET was acquired before and 12 months after SABR. Pre- and post-treatment [18F] NaF-PET images were registered to the treatment planning CT. The relative change in tumour SUVmax and SUVmean was quantified. The intersection of each of the radiation therapy isodose contours with a non-tumour bone was created. The change in SUVmean in sub-volumes of non-tumour bone receiving doses of 0-20 Gy was quantified. In total, 14 patients, with 17 bone metastases, were available for analysis. A total of 15 metastases exhibited a reduction in SUVmax; the median reduction was 42% and the maximum reduction 82%. An increased absolute reduction in SUVmax was observed with higher pre-treatment SUVmax. One patient exhibited increased SUVmax after treatment, which was attributed to normal peri-tumoural bone regeneration in the context of a bone metastasis. There was a median reduction of 15%-34% for non-tumour bone in each dose level. [ABSTRACT FROM AUTHOR]

Background: Metabolic reprogramming is one of the hallmarks of cancer, and in breast cancer (BC), several metabolic enzymes are overexpressed and overactivated. One of these, Enolase 1 (ENO1), catalyses glycolysis and is involved in the regulation of multiple signalling pathways. Objectives: This study aimed to evaluate in silico the prognostic and predictive effects of ENO1 expression in BC. Design: This is a bioinformatic in silico analysis. Methods: Using available online platforms (Kaplan–Meier [KM] plotter, receiver operating characteristic curve [ROC] plotter, cBioPortal, Genotype-2-Outcome [G-2-O], MethSurv, and Tumour–Immune System Interaction Database [TISIDB]), we performed a bioinformatic in silico analysis to establish the prognostic and predictive effects related to ENO1 expression in BC. A network analysis was performed using the Oncomine platform, and signalling, epigenetic, and immune regulation pathways were explored. Results: ENO1 was overexpressed in all the analysed Oncomine, epigenetic, and immune pathways in triple-negative, but not in hormone receptor–positive BCs. In human epidermal growth factor receptor 2 (HER2)-positive BCs, ENO1 expression showed a mixed profile. Analysis on disease progression and histological types showed ENO1 overexpression in ductal in situ and invasive carcinoma, in high-grade tumours followed by advanced or metastasis and was linked to worse survival. High ENO1 expression was also associated with relapse-free, distant metastasis-free and overall survival, irrespectively of treatment and was mainly related to basal subtype. Conclusion: ENO1 overexpression recruits a range of signalling pathways during disease progression conferring a worse prognosis and can be potentially used as a biomarker of disease progression and therapeutic target, particularly in triple-negative and in ductal invasive carcinoma. [ABSTRACT FROM AUTHOR]

Background: Solid tumors often develop hypoxic regions, leading to aggressive behavior and increased drug resistance. Methods: The chemical composition of Cymbopogon citratus essential oil (EO) was analyzed using GC-MS. Alginate nanoparticles containing the EO and its primary component, citral, were synthesized via the ionic gelation method. Encapsulation was confirmed using ATR-FTIR analysis. The anticancer efficacy of C. citratus EO, citral, and their respective alginate nanoparticles was evaluated under normoxic (21% oxygen) and hypoxic (1% oxygen) conditions on breast cancer (MDA-MB-231) and melanoma (A-375) cell lines. Additionally, qPCR and flow cytometry were used to assess apoptosis gene expression ratios (Bax/Bcl-2) and levels of apoptosis. Results: Citral (80.98%) was identified as the major component of the EO. Alginate nanoparticles containing C. citratus EO and citral (C. citratus-AlgNPs and citral-AlgNPs) were synthesized with particle sizes of 195 ± 4 nm and 222 ± 9 nm, and zeta potentials of -22 ± 3 mV and − 17 ± 1 mV, respectively. Both samples demonstrated significantly greater efficacy under hypoxic conditions. Citral and C. citratus-AlgNPs had IC50 values of 27 (19–39) µg/mL and 25 (4-147) µg/mL, respectively, against MDA-MB-231 and A-375 cells. Flow cytometry showed increased apoptosis under hypoxic conditions, with the highest rates observed for citral-AlgNPs and C. citratus-AlgNPs (84 ± 5 and 92 ± 5% in MDA-MB-231 and A-375 cells, respectively). Conclusion: This study demonstrates that alginate nanoparticles enhance the anticancer activity of C. citratus-AlgNPs and citral, particularly under hypoxic conditions, highlighting their potential for hypoxia-targeted cancer therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer has a high predilection for intracranial metastases, second only to lung cancer. The development of intracranial metastases adds significant morbidity and mortality, with the treatment paradigm evolving greatly over the past two decades. The emergence of stereotactic radiosurgery has allowed for the delivery of a highly conformal tumoricidal dose, providing optimal local control while minimizing neurocognitive impairment. Although SRS has demonstrated effectiveness in treating brain metastases, there is significant variability in the methodologies and patient populations across studies focusing on its application for intracranial metastases originating from breast cancer. We conducted a meta-analysis to better understand the impact of stereotactic radiosurgery on the management of intracranial metastases from breast cancer. Background/Objectives: To determine the impact of stereotactic radiosurgery on outcomes of metastatic breast cancer with intracranial metastases. Methods: We systematically searched the PubMed and EMBASE databases for studies published between 1 January 1990 and 1 August 2024. Primary research articles evaluating the outcomes of stereotactic radiosurgery on intracranial metastases from breast cancer were included. Adverse events were defined as leptomeningeal disease, radiation necrosis, seizure, and headache. The pooled estimate was calculated using the DerSimonian and Laird approach. Results: Sixteen studies encompassing 1228 patients met the inclusion criteria. Our analysis revealed a median survival duration of 13.1 ± 3.8 months and a pooled 1-year overall survival rate of 53.1% after SRS treatment. There was a 29% local recurrence rate at 1 year and a 35% overall distant recurrence rate. In addition, our analysis found a relatively low rate of acute adverse events at 15.5%. Conclusions: SRS demonstrates promising efficacy and safety in managing intracranial metastases from breast cancer, with a favorable toxicity profile. [ABSTRACT FROM AUTHOR]

Simple Summary: Almost one in five patients with breast cancer have an aggressive subtype that expresses Human Epidermal Growth Factor-2 (HER2) receptor. The introduction of anti-HER2 therapy, like trastuzumab and pertuzumab, has dramatically improved treatment outcomes. However, such therapy is lengthy, costly, and can result in substantial cardiac toxicities. In this review, we discuss ways to de-escalate anti-HER2 therapy by shortening the treatment course to less than the 12-month standard, or minimizing companion chemotherapy. New molecular tools are emerging that should help physicians select which patients with HER2-positive breast cancer benefit most from aggressive and lengthy treatment regimens utilizing single or dual anti-HER2 therapy alone or in combination with chemotherapy. Almost one-fifth of breast cancer cases express Human Epidermal Growth Factor-2 (HER2), and such expression is associated with highly proliferative tumors and poor prognosis. The introduction of anti-HER2 therapies has dramatically changed the natural course of this aggressive subtype of breast cancer. However, anti-HER2 therapy can be associated with substantial toxicities, mostly cardiac, and high cost. Over the past few years, there has been growing interest in de-escalation of anti-HER2 therapies to minimize adverse events and healthcare costs, while maintaining the efficacy of treatment. Data from clinical observations and single-arm studies have eluted to the minimal impact of anti-HER2 therapy in low-risk patients, like those with node-negative and small tumors. Though single-arm, the APT trial, in which patients with node-negative, small tumors received single-agent paclitaxel for 12 cycles plus trastuzumab for 1 year, was a practice-changing study. Several other recently published studies, like the PERSEPHONE trial, have shown more convincing data that 6 months of trastuzumab is not inferior to 12 months, in terms of disease-free survival (DFS), suggesting that de-escalating strategies with shorter treatment may be appropriate for some low-risk patients. Other de-escalating strategies involved an adaptive, response-directed approach, and personalized therapy that depends on tumor genomic profiling. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is one of the leading causes of death, with one out of six deaths worldwide. Breast cancer has the highest occurrence of other cancers, although, in terms of the number of deaths, breast cancer ranks fifth among all cancers. Depending on the nature of the cells and the associated cellular environment, different types of breast cancer are possible. Many breast cancer types are highly challenging to treat, and even if treatable, the treatments involve several side effects. Antibody–drug conjugates (ADCs) comprise monoclonal antibodies that explicitly target the tumor-specific antigens and cytotoxic drugs (mainly small molecules) that act as payloads to kill the malignant cells/tumor. As a result, the healthy cells are not affected by the toxic drugs, which potentially reduces the side effects. These target-specific chemo-biologic drugs (ADCs) have shed new light on hopes in cancer therapy. Currently, three ADCs have been approved for breast cancer treatment, and many are in clinical trials. A detailed discussion on the biochemical nature, mechanism of action, and current status of ADCs in breast cancer treatments has been accomplished in this article. While we made every effort to include all the related developments in this field, any omission is truly unintentional. Cancer is a significant health challenge globally, with millions of people affected every year, resulting in high morbidity and mortality. Although other treatment options are available with limitations, chemotherapy, either standalone or combined with other therapeutic procedures, is the most commonly used practice of treating cancer. In chemotherapy, cancer cells/malignant tumors are targeted; however, due to less target specificity, along with malignant cells, normal cells are also affected, which leads to various off-target effects (side effects) that impact the patient quality of life. Out of all the different types of cancers, breast cancer is the most common type of cancer in humans worldwide. Current anticancer drug discovery research aims to develop therapeutics with higher potency and lower toxicity, which is only possible through target-specific therapy. Antibody–drug conjugates (ADCs) are explicitly designed to target malignant tumors and minimize off-target effects by reducing systemic cytotoxicity. Several ADCs have been approved for clinical use and have shown moderate to good efficacy so far. Considering various aspects, chemotherapy and ADCs are useful in treating cancer. However, ADCs provide a more focused and less toxic approach, which is especially helpful in cases where resistance to chemotherapy (drug resistance) occurs and in the type of malignancies in which specific antigens are overexpressed. Ongoing ADC research aims to develop more target-specific cancer treatments. In short, this study presents a concise overview of ADCs specific to breast cancer treatment. This study provides insight into the classifications, mechanisms of action, structural aspects, and clinical trial phases (current status) of these chemo-biologic drugs (ADCs). [ABSTRACT FROM AUTHOR]

Simple Summary: Obesity increases the risk of several cancers, including breast cancer. With global obesity rates rising, it is important to understand how excess fat accumulation influences cancer development and progression. This study examined how overweight/obesity affects the breast adipose tissue around triple-negative breast cancer (TNBC), a particularly aggressive type of breast cancer. Therefore, tissue samples from overweight/obese and normal weight patients with TNBC were compared. We found that overweight/obese TNBC patients had larger fat cells, more immune cells that could support cancer growth, and fewer cells related to new blood vessel formation in the tumor-surrounding environment. Overweight/obese patients also showed higher numbers of special fibroblast cells with potential tumor-promoting functions. Moreover, tumor cells at the invasive front, which are in close contact with fat cells, showed higher levels of proteins that metabolize fatty acids, suggesting altered lipid handling in cancer cells in overweight/obese TNBC patients. Together, these findings imply that obesity is associated with distinct changes in the tumor-adjacent adipose tissue in TNBC, potentially affecting cancer aggressiveness. Understanding these changes may help to develop more effective treatment strategies for obese TNBC patients, which may improve their prognosis and overall health outcomes. Background: Obesity is a risk factor of several types of cancer, including breast cancer. In this study, we aimed to histologically characterize the adipose tissue of the tumor microenvironment (TME) of triple-negative breast cancer (TNBC) in overweight/obese versus normal-weight patients. Methods: TNBC tissue sections from normal-weight (BMI<25) and overweight/obese patients (BMI≥25) were stained with antibodies against CD68, CD163, CD31, CD34, and vimentin. At the invasive tumor front, positive cells were counted in tumor adjacent adipose tissue (AT) and within cancer tissue (CT). Further, the size of the tumor-adjacent and distant mammary adipocytes was determined in perilipin stained sections. Expression of ANGPTL4, CD36 and FABP4, proteins involved in fatty acid metabolism, was analyzed in marginal tumor cells using an immune reactive score. Results: Overweight/obese TNBC patients had significantly larger adipocytes, higher numbers of CD163+ macrophages (BMI<25: 2.80 vs. BMI≥25: 10.45; p = 0.011) and lower numbers of CD31+ (BMI<25: 4.20 vs. BMI≥25: 2.40; p = 0.018) and CD34+ (BMI<25: 14.60 vs. BMI≥25: 5.20; p = 0.045) cells as markers of angiogenesis in the AT as well as a higher frequency of cancer-associated-fibroblast-like cells in the AT and CT (BMI<25: 7.60 vs. BMI≥25: 25.39 in total; p = 0.001). Moreover, expression of CD36 (BMI<25: 2.15 vs. BMI≥25: 2.60; p = 0.041) and ANGPTL4 (BMI<25: 6.00 vs. BMI≥25: 9.80; p = 0.026) was elevated in the TNBC cells of overweight/obese patients. Conclusions: Our data suggest BMI-related changes in the TME of overweight/obese TNBC patients, including hypertrophied adipocytes, reduced vascularization, more M2-like macrophages and CAF-like cells, and an increase in the expression of fatty acid metabolizing proteins in marginal tumor cells, all contributing to a more tumor-promoting, immunosuppressive environment. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiologists often call back women whose screening mammograms show features that are suggestive of breast cancer for additional testing. Imaging modalities used for the additional testing of these women vary across countries and screening services; however, we do not know the imaging modality that best distinguishes between women who have and those who do not have breast cancer. We examined published studies to identify the best imaging modality that can be used for the testing of women who are recalled following mammography screening. We collected and analysed all the results in the studies published to date. Our analysis showed that contrast-enhanced mammography, digital breast tomosynthesis, magnetic resonance imaging, and ultrasound perform better than digital mammography in correctly identifying and classifying cancer lesions referred for additional testing; however, digital breast tomosynthesis and digital mammography perform better in correctly dismissing women who do not have cancer. There are variations in the assessment pathways for women recalled at screening, and the imaging assessment pathway with the best diagnostic outcome is poorly understood. This paper examines the efficacy of five imaging modalities for the assessment of screen-recalled breast lesions. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) strategy was employed to identify studies that assessed the efficacy of imaging modalities in the assessment of lesions recalled at screening from the following eight databases: Medline, Web of Science, Embase, Scopus, Science Direct, PubMed, CINAHL, and Global Health. Search terms included "Breast assessment" AND "Diagnostic Workup" OR "Mammography" AND "Digital Breast tomosynthesis" AND "contrast enhanced mammography and Magnetic Resonance imaging" AND "breast ultrasound". Studies that examined the performance of digital mammography (DM), digital breast tomosynthesis (DBT), handheld ultrasound (HHUS), contrast-enhanced mammography (CEM), and magnetic resonance imaging (MRI) in screen-recalled lesions were reviewed. Meta-analyses of these studies were conducted using the MetaDisc 2.0 software package. Results: Fifty-four studies met the inclusion criteria and examined between one and three imaging modalities. Pooled results of each imaging modality demonstrated that CEM has the highest sensitivity (95; 95% CI: 90–97) followed by MRI (93; 95% CI: 88–96), DBT (91; 95% CI: 87–94), HHUS (90; 95% CI: 86–93), and DM (85; 95% CI: 78–90). The DBT demonstrated the highest specificity (85; 95% CI: 75–91) followed by DM (77; 95% CI: 66–85), CEM (73; 95% CI: 63–81), MRI (69; 95% CI: 55–81), and HHUS (65; 95% CI: 46–80). Conclusions: The CEM, MRI, DBT, and HHUS demonstrate excellent performance in correctly identifying and classifying cancer lesions referred for diagnostic work-up, but HHUS, MRI, and CEM have a more limited ability to discriminate benign lesions than DBT and DM. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to assess the impact of various factors—such as age, age at menarche, age at first childbirth, number of births, body mass index (BMI), living environment (rural vs. urban), and other factors later discussed—on the likelihood of developing breast cancer. This article's original research was based on data gathered from 687 breast biopsies, which were analyzed through comparative analysis and regression analysis to identify possible predictors for malignancy and tumor size. The comparative analysis and regression models in this study provide deeper insights into the roles of various variables, particularly positive hormonal receptor status, in malignancy. Introduction: Breast cancer has become one of the most serious and widespread public health concerns globally, affecting an increasing number of women—and, in rare cases, men—across the world. It is the most common cancer among women across all countries. In this study, we aimed to evaluate the influence of demographic factors, medical and reproductive history, diagnostic techniques, and hormone receptor status on the development and progression of breast cancer. Materials and Methods: A total of 687 female patients from Romania underwent standard breast examination techniques, including clinical breast examination, mammography, ultrasonography, and, ultimately, breast biopsy. Statistical analysis was performed using the R programming language and RStudio software. The study included a comparative analysis and a prediction analysis for malignancy and tumor size (cumulative histological dimension) through logistic and linear regression models. Results: The comparative analysis identified several variables associated with malignancy: older age (p < 0.001), non-vulnerability (p = 0.04), no daily physical activity (p = 0.002), no re-biopsy (p < 0.001), immunohistochemistry use (p < 0.001), use of larger gauge needles (p < 0.001), ultrasound-guided biopsy (p < 0.001), and vacuum biopsy (p < 0.001). The hormone receptor statuses—estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR)—showed statistically significant differences in distribution across breast cancer B classifications. Logistic regression analysis identified ER, PR, and age as significant predictors of malignancy. Linear regression analysis revealed histopathological results, living environment, geographical region, vulnerability, prior breast examination, and the number of histological fragments as significant predictors of cumulative histological dimension. Conclusions: Our predictive models demonstrate the impact of demographic factors, medical history, diagnostic techniques, and hormone receptor status on breast cancer development and progression, accounting for a significant portion of the variance in malignancy and cumulative histological dimension. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer continues to represent a leading cause of death among women globally. Recent studies have shown a growing link between breast cancer and the living microorganisms from the tumoral breast tissue, known as microbiota. This review looks at how the microbiota is found in healthy breast tissue and the changes observed during cancer development and progression. The microbiota has been shown to affect cancer growth, spread, and resistance to treatments by interacting with the tumor's environment. Moreover, this review explores how different breast cancer types have distinct microbial profiles. Future studies could improve breast cancer care by endowing the microbiota as a diagnostic, prediction and treatment marker. Breast cancer remains one of the leading causes of death among women worldwide, and recent research highlights its growing connection to alterations in the microbiota. This review delves into the intricate relationship between microbiotas and breast cancer, exploring its presence in healthy breast tissue, its changes during cancer progression, and its considerable impact on both the tumor microenvironment (TME) and the tumor immune microenvironment (TIME). We extensively analyze how the microbiota influences cancer growth, invasion, metastasis, resistance to drugs, and the evasion of the immune system, with a special focus on its effects on the TIME. Furthermore, we investigate distinct microbial profiles associated with the four primary molecular subtypes of breast cancer, examining how the microbiota in tumor tissues compares with that in adjacent normal tissues. Emerging studies suggest that microbiotas could serve as valuable diagnostic and prognostic biomarkers, as well as targets for therapy. This review emphasizes the urgent need for further research to improve strategies for breast cancer prevention, diagnosis, and treatment. By offering a detailed examination of the microbiota's critical role in breast cancer, this review aims to foster the development of novel microbiota-based approaches for managing the disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Pericardial disease is a common and severe complication in patients with cancer, often presenting as acute pericarditis, pericardial effusion, or constrictive pericarditis. Causes include direct tumor invasion, metastasis, and cancer treatments like chemotherapy and radiotherapy. Lung cancer is the most frequent etiology, followed by breast cancer and lymphomas. Early detection and multidisciplinary management are crucial. Acute pericarditis requires careful diagnosis and treatment with NSAIDs and colchicine. Pericardial effusion is commonly incidental but can lead to cardiac tamponade, necessitating pericardiocentesis or a pericardial window. Immunotherapy-related effusions typically respond to treatment cessation and steroids. Constrictive pericarditis, although rare, requires prompt diagnosis and may necessitate surgical intervention. Multidisciplinary care and early intervention are vital for improving patient outcomes and quality of life. Pericardial disease is increasingly recognized in cancer patients, including acute pericarditis, pericardial effusion, and constrictive pericarditis, often indicating a poor prognosis. Acute pericarditis arises from direct tumor involvement, cancer therapies, and radiotherapy. Immune checkpoint inhibitor (ICI)-related pericarditis, though rare, entails significant mortality risk. Treatment includes NSAIDs, colchicine, and corticosteroids or anti-IL1 drugs in refractory cases. Pericardial effusion is the most frequent manifestation, primarily caused by lung cancer, followed by breast cancer, lymphoma, leukemia, gastrointestinal tumors, and melanoma. Chemotherapy, immunotherapy, and radiotherapy may also cause fluid accumulation in the pericardial space. Symptomatic relief for pericardial effusion may require pericardiocentesis, prolonged catheter drainage, or a pericardial window. Instillation of intrapericardial cytostatic agents may reduce recurrence. Constrictive pericarditis, though less common, often develops from radiotherapy and requires multimodality imaging for diagnosis, with pericardiectomy as the definitive treatment. Primary pericardial tumors are rare, with metastases being more frequent. Patients with cancer and pericardial disease generally have poor survival, emphasizing the need for early detection. A multidisciplinary approach involving hematologists, oncologists, and cardiologists is crucial to tailoring pericardial disease treatment to a patient's clinical status, thereby improving the quality of life and prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is a complex disease with several subtypes that impact different populations in various ways. This study focuses on the diverse ethnic population of Hawai'i. We aim to investigate whether there are differences in breast cancer subtypes among various racial and ethnic groups that could contribute to disparities in breast cancer outcomes. This study analyzes the incidence and prevalence of breast cancer subtypes in these groups, considering factors such as age and tumor biology. By identifying subtype-specific risks and outcomes, we hope to provide insights that could lead to more tailored and effective treatments, thereby improving prognosis and reducing mortality disparities in diverse communities. Our findings have important implications for clinical practice in regions with diverse populations. This study highlights the need for more individualized approaches to breast cancer screening and treatment to improve patient outcomes. Background: Differences in the incidence of breast cancer subtypes among racial/ethnic groups have been evaluated as a contributing factor in disparities seen in breast cancer prognosis. We evaluated new breast cancer cases in Hawai'i to determine if there were subtype differences according to race/ethnicity that may contribute to known disparities. Methods: We reviewed 4591 cases of women diagnosed with breast cancer from two large tumor registries between 2015 and 2022. We evaluated breast cancer cases according to age at diagnosis, self-reported race, breast cancer subtype (ER, PR, and HER2 receptor status), histology, county, and year. Results: We found both premenopausal and postmenopausal Native Hawaiian women were less likely to be diagnosed with triple-negative breast cancer (OR = 0.26, 95% CI 0.12–0.58 p = 0.001; OR = 0.54, 95% CI 0.36, 0.80 p = 0.002, respectively). Conclusions: The results of our study support that there are racial/ethnic differences in breast cancer subtypes among our population, which may contribute to differences in outcomes. Further evaluation of clinical and pathological features in each breast cancer subtype may help improve the understanding of outcome disparities seen among different racial/ethnic groups. [ABSTRACT FROM AUTHOR]

Simple Summary: It was shown for the first time that the salivary levels of the MUC1 family, including CA 15-3, CA 27.29, and MCA, were significantly dependent on the expression of human epidermal growth factor receptor 2 (HER2) in breast cancer patients. In the presence of HER2 expression, mucin levels decreased with a simultaneous decrease in the levels of free estrogen and progesterone and an increase in the content of pro-inflammatory cytokines and free amino acids, which was consistent with the aggressive growth pattern and high invasiveness of HER2-positive breast cancer subtypes. The MUC1 family of transmembrane glycoproteins (CA 15-3, CA 27.29, MCA) is aberrantly expressed among patients with breast cancer. Objectives: to measure the level of degradation products of MUC1, including CA 15-3, CA 27.29, and MCA, in the saliva of breast cancer patients and to describe the biochemical processes that influence their expression and the regulation of their biological functions. Methods: The case–control study included three groups (breast cancer, fibroadenomas, and healthy controls). All study participants provided saliva samples strictly before starting treatment. The levels of MUC1, including CA 15-3, CA 27.29, and MCA, free progesterone and estradiol, cytokines (MCP-1, VEGF, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18), and amino acids (Asp, Gln, Gly, His, Leu + Ile, Orn, Phe, Pro, Tyr) were determined. Results: It was shown that the levels of the MUC1 family in the saliva of patients with HER2-positive breast cancer were significantly lower compared to the control group. The level of pro-inflammatory cytokines and the level of free estradiol affected the expression of MUC1. We obtained a reliable relationship between the aggressive nature of tumor growth, an increased level of pro-inflammatory cytokines, a low level of free estradiol, and the suppressed expression of salivary MUC1. Conclusions: Among patients with aggressive breast cancer, a high level of pro-inflammatory cytokines, and a low level of free estradiol, there was an inhibition of the expression of pathologically unchanged glycoprotein MUC1 in saliva. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the effectiveness and safety of a common breast cancer treatment in elderly patients, a group often overlooked in clinical trials. Specifically, it focuses on using CDK4/6 inhibitors with hormone therapy for treating metastatic HR+/HER2- breast cancer in patients aged 70 and older. This research aims to understand how well this treatment works and how tolerable it is for this vulnerable population, which faces unique challenges due to age and other health conditions. The results of this study may provide valuable insights for clinicians, enabling more informed treatment decisions which optimize therapeutic outcomes and enhance the quality of life for elderly patients with breast cancer. Background: Metastatic HR+/HER2- breast cancer is commonly treated with CDK4/6 inhibitors in combination with endocrine therapy. However, the efficacy and safety of this approach in elderly patients (≥70 years) remain unclear, particularly in the context of real-world clinical practice. This study aims to evaluate the clinical outcomes and tolerability of CDK4/6 inhibitor treatments in this fragile population, which is often under-represented in randomized clinical trials. Patients and methods: This retrospective multicenter study included elderly patients with metastatic HR+/HER2-negative breast cancer receiving first-line CDK4/6 inhibitors. The primary endpoint was progression-free survival (PFS). The secondary endpoints focused on the overall survival (OS), safety, and tolerability, considering variables such as tumor subtype, age, comorbidities, and treatment specifics. Results: The median PFS and OS were slightly lower than those reported in clinical trials, reflecting the inclusion of a more fragile population. The luminal B subtype was linked to a poorer PFS, while other factors like age, BMI, and ECOG status did not significantly affect the outcomes. A safety analysis indicated a higher incidence of grade 3 or higher toxicities, especially in frail patients, leading to dose reductions. Despite these challenges, CDK4/6 inhibitors were generally well-tolerated, allowing most patients to continue therapy. Conclusions: CDK4/6 inhibitors with endocrine therapy are effective in elderly patients with metastatic HR+/HER2- breast cancer, though careful management is crucial to balance efficacy and minimize adverse events. [ABSTRACT FROM AUTHOR]

Background: Today, breast cancer is the most diagnosed cancer worldwide. There are many different clinical presentations, radiological characteristics, and histological types of breast cancer. HER2 is overexpressed in a significant number of breast cancer cases reaching 20% of all breast cancers, and its overexpression is seen directly proportionate with a poor outcome and prognosis. Methods: We started this cross-sectional research from January 2022–December 2023 on 202 breast cancer patients who had 220 lesions. The molecular subtypes of the different lesions were determined in all the included cases. Magnetic resonance imaging (MRI) studies were conducted in all included cases. The MRI parameters included conventional MRI, diffusion-weighted analysis, and dynamic post-contrast T1-weighted imaging. Results: The prevalence of irregular margins (P < 0.001), linear and segmental distribution (P = 0.044), heterogeneous pattern (P < 0.001), and type 2 curve was statistically significantly higher in the HER2-positive lesions. Nipple infiltration incidence showed statistically significant elevation in the HER2-positive lesions (P = 0.017). The lesions' ADC and perilesional ADC in the HER2-positive lesions were also statistically significantly elevated. The best cutoff point of ADC to detect lesions with positive HER2 expression was > 0.885 × 10–3 mm2/s, with 65.7% sensitivity and 60% specificity, with a statistically significant value (p = 0.005). Conclusions: Magnetic resonance imaging of breast imaging is a promising noninvasive method for identifying breast tumors with the HER2 molecular subtype. Combining various radiological features by MRI may provide a conclusion for recognizing positive HER2 lesions. [ABSTRACT FROM AUTHOR]

Intraoperative surgical margin assessment remains a challenge during breast-conserving surgery. Here, we report a combined strategy of immuno–positron emission tomography (PET) for preoperative detection of breast cancer and guided assessment of margins in breast-conserving surgery through second near-infrared (NIR-II) fluorescence imaging of trophoblastic cell surface antigen 2 (TROP2). We demonstrated that the intensity of PET signals in the tumors was nearly five times higher than in normal breast tissue with a zirconium-89 tracer conjugated to sacituzumab govitecan (SG) in a mouse spontaneous breast cancer model, enabling the identification of tumors. We further generated a NIR-II probe of indocyanine green conjugated to SG (ICG-SG) and developed a rapid incubation imaging method for intraoperative margin assessment in a relevant time window for the operation workflow. The ICG-SG NIR-II fluorescence image guidance was first verified to remove tumors completely and accurately in mouse breast cancer models. Moreover, the rapid incubation imaging method was applied to distinguish benign and malignant breast lesions in samples from 26 patients with breast cancer. Therefore, we have developed both nuclide and optical probes targeting TROP2 for rapid and precise identification of tumor margins during breast-conserving surgery in humans. Editor's summary: Identification of tumor borders is essential for effective surgical management of breast cancer. TROP2 is expressed in breast tumors but not normal mammary tissues. Here, Chen et al. developed imaging probes with the TROP2-targeted sacituzumab govitecan (SG) antibody-drug conjugate to assist surgeons in determining tumor versus normal mammary tissues before and during surgery. Labeling of SG with the near-infrared (NIR) fluorophore indocyanine green (ICG) supported the identification of TROP2+ tumor margins in NIR-II–guided surgery in murine breast tumor models. A rapid ex vivo tissue staining method with SG-ICG was also developed to intraoperatively evaluate TROP2+ tumor margins during human breast-conserving surgery. TROP2 probes are a promising approach for improving surgical removal of breast tumors. —Molly Ogle [ABSTRACT FROM AUTHOR]

Open nanoshells such as nanobowls or nanocups collectively described as 'semi shells' have unique plasmonic properties due to their lack of symmetry. So far, their fabrication was based on multistep and laborious methods such as solid state sputter coating or selective deposition/etching using sacrificial templates. In this work, we report a rapid one step colloidal synthetic protocol for PEGylated semi-shell (SS) fabrication by simultaneous facet specific anisotropic chemical etching of rhombic dodecahedral ZIF-8 and heterogenous nucleation & growth of gold. The SS possesses a strong localized surface plasmon resonance in the near-infrared region, which is retained after surface passivation with polyethylene glycol and subsequent cryopreservation for extended shelf-life. Freshly reconstituted PEGylated SS was found to be safe & non-toxic in healthy C57BL/6 mice post intravenous administration. The PEGylated SS displayed significant photothermal efficiency of ~37% with 808 nm laser irradiation. Preclinical assessment of intra-tumoral photothermal efficacy indicated complete remission of primary breast tumor mass with insignificant metastasis to vital organs in 4T1 FL2 tumor bearing CD1 nude mice. Further, PEGylated SS mediated photothermal therapy also yielded morbidity free survivael of 75% for up to 90 days, indicating their potential to significantly improve outcomes in advanced breast tumors. Anisotropic gold-based colloidal nanoparticles such as semi shells have unique optical properties and widespread applications such as in bioimaging, biosensing and therapy, however, the fabrication process of semi shells remains a challenge due to laborious multistep solid state and colloidal procedures. In this study, the authors develop a rapid one-pot colloidal synthetic route for the fabrication of semi shells using ZIF-8 as a sacrificial template, and demonstrate their promise for photothermal therapy. [ABSTRACT FROM AUTHOR]

Background: Numerous underlying causes can lead to inflammatory breast disorders. A wide range of non-specific symptoms may be presenting symptoms, which could cause a delay in diagnosis and thus improper therapy. Studies on artificial intelligence (AI) are rapidly developing and offer a wide range of possible uses in breast imaging. Artificial intelligence-based computer-assisted diagnosis (AI-CAD) holds promise in the field of mammography. It demonstrated diagnostic performances that are equivalent to or even better than those achieved by stand-alone methods. The current work aimed to identify whether AI can improve the performance of mammography in diagnosing inflammatory breast diseases and excluding the underlying malignancy in cases resistant to treatment that may reduce the need for interventional procedures such as biopsy. Methods: Our study was a retrograde one done on 34 patients with pathologically proven inflammatory breast lesions. Results: Suppurative breast lesions gave high false positive results. This was also the case with granulomatous mastitis; while simple inflammatory lesions gave true negative results on AI interrogation. Conclusions: Artificial intelligence can be of great value in diagnosing simple inflammatory breast lesions thus following up on such lesions can usually be sufficient without asking for unneeded biopsies. On the other hand, our study showed that AI had high false positive results in suppurative lesions and granulomatous mastitis. Consequently, ultrasonography can be more reliable in their diagnosis. [ABSTRACT FROM AUTHOR]

Background: Electronic Patient-Reported Outcome Measures (ePROMs) have emerged as valuable tools in cancer care, facilitating the comprehensive assessment of patients' physical, psychological, and social well-being. This study synthesizes literature on the utilization of ePROMs in oncology, highlighting the diverse array of measurement instruments and questionnaires employed in cancer patient assessments. By comprehensively analyzing existing research, this study provides insights into the landscape of ePROMs, informs future research directions, and aims to optimize patient-centred oncology care through the strategic integration of ePROMs into clinical practice. Methods: A systematic review was conducted by searching peer-reviewed articles published in academic journals without time limitations up to 2024. The search was performed across multiple electronic databases, including PubMed, Scopus, and Web of Science, using predefined search terms related to cancer, measurement instruments, and patient assessment. The selected articles underwent a rigorous quality assessment using the Mixed Methods Appraisal Tool (MMAT). Results: The review of 85 studies revealed a diverse range of measurement instruments and questionnaires utilized in cancer patient assessments. Prominent instruments such as the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Patient Reported Outcome-Common Terminology Criteria for Adverse Events (PROCTCAE) were frequently referenced across multiple studies. Additionally, other instruments identified included generic health-related quality of life measures and disease-specific assessments tailored to particular cancer types. The findings indicated the importance of utilizing a variety of measurement tools to comprehensively assess the multifaceted needs and experiences of cancer patients. Conclusion: Our systematic review provides a comprehensive examination of the varied tools and ePROMs employed in cancer care, accentuating the perpetual requirement for development and validation. Prominent instruments like the EORTC QLQ-C30 and PRO-CTCAE are underscored, emphasizing the necessity for a thorough assessment to meet the multifaceted needs of patients. Looking ahead, scholarly endeavours should prioritize the enhancement of existing tools and the creation of novel measures to adeptly address the evolving demands of cancer patients across heterogeneous settings and populations. [ABSTRACT FROM AUTHOR]

Background: Results from studies investigating the association between ultra-processed foods (UPFs) and breast cancer are scarce and, in some cases, contradictory. Therefore, we aimed to evaluate the association between the intake of processed foods (PFs) and UPFs with the risk of breast cancer in Iranian women. Methods: The present case (n = 133) - control (n = 266) study was carried out at two general hospitals in Tehran, Iran. A 168-item semi-quantitative food frequency questionnaire was used to assess the participants' dietary intake. Also, the NOVA classification was used to identify PFs and UPFs. The association between PFs and UPFs with the odds of breast cancer was analyzed using logistic regression models. Results: According to Model 1 of conditional logistic regression, the odds of breast cancer were higher in the last tertile of UPFs than in the first tertile (odds ratio (OR) = 1.930; 95% confidence interval (CI): 1.080–3.449). In Model 2, no significant association was observed between the second and last tertiles of PFs and UPFs with the odds of breast cancer compared to the reference tertile. Also based on menopause status, the odds of breast cancer increased in the last tertile only among premenopausal women in Model 2 (OR = 3.656; 95% CI: 1.326–10.079). Conclusions: This study demonstrated that higher consumption of UPFs is associated with higher odds of breast cancer in premenopausal women. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is a breast malignancy with a poor prognosis and limited therapeutic options. Many studies show that TNBC exhibits heterogeneity across clinical, histopathological, and molecular levels. In this review, we discuss the immunogenic features of TNBC with a focus on immunotherapy and the current standard of care in the neoadjuvant, adjuvant, and metastatic setting. In addition, we address the ongoing research on immunotherapy, antibody‐drug conjugates (ADCs), poly ADP‐ribose polymerase (PARP) inhibitors, and future challenges in the treatment of this entity. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by poor prognosis due to the absence of effective targeted therapies. Emerging evidence indicates that the gut microbiota and its metabolites play a key role in the occurrence and development of TNBC. This study aimed to explore the metabolic changes and potential mechanisms associated with TNBC. Objectives: This study aimed to explore the potential relationship between targeted metabolites and the gut microbiota in TNBC. Design: We recruited 8 participants, including 4 with TNBC and 4 with benign fibroadenomas as controls. Methods: The gut microbiota was analyzed using metagenomics on fecal samples. Liquid chromatography–mass spectrometry (LC-MS) was employed to identify differential metabolites in serum and fecal samples. The correlation between the gut microbiota and metabolites was analyzed using Spearman's correlation analysis. Results: Analysis of altered serum metabolites in the TNBC group revealed changes, particularly in carboxylic acids and derivatives, benzene, and substituted derivatives. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis revealed significant enrichment in 18 pathways. Regarding fecal metabolites, differences between the 2 groups also included carboxylic acids and derivatives, benzene, and substituted derivatives, with 28 metabolic pathways enriched based on KEGG pathway analysis. Metagenomics analysis showed differences in the relative abundance of Anaerococcus, Fischerella, and Schizosaccharomyces at the genus level, which have been previously associated with breast cancer. Furthermore, 4 serum metabolites—L-glutamine, citrate, creatinine, and creatine—along with 9 fecal metabolites, were associated with the aforementioned microbiota. Conclusion: Our findings highlight distinct metabolite profiles in the serum and feces of patients with TNBC. The identification of gut microbiota and their associated metabolites provides new insights into the pathophysiological mechanisms underlying TNBC. [ABSTRACT FROM AUTHOR]

Background: Bone metastases are common in patients with progressive cancer and often present in long bones, leading to adverse events such as pathologic fractures. In the acute care setting, physical therapists (PTs) may be the initial providers who identify symptoms associated with fracture risk and communicate concerns to help prevent such adverse events. Case description: A 39-year-old female patient with metastatic breast cancer was admitted to the hospital due to uncontrolled pain. She had a history of bone metastases to the left femur; however, no restrictions or precautions were noted during the initial PT examination. During this initial PT examination, she reported worsening hip pain with weight-bearing activities. Outcomes: With the PT's recognition of red flag symptoms, an MRI was completed, which revealed extensive metastatic disease in her left femur with concern for an imminent fracture; as a result, prophylactic fixation was performed. Her functional abilities improved after surgery and consistent therapeutic intervention, allowing her to achieve a level of independence sufficient to return home safely. Discussion and conclusion: This case demonstrates the successful identification of imminent fracture risk by a PT in a patient with metastatic breast cancer, as well as the therapeutic management that accompanied this process in the acute care setting. [ABSTRACT FROM AUTHOR]

Background: Myeloid Derived Suppressor Cells (MDSCs) are capable of inhibiting both innate and adaptive immune responses and accumulate in the microenvironment of breast tumors. Hence, MDSC depletion by chemotherapeutic agents can improve clinical efficacy of cancer immunotherapy. The effects of 5-FU and doxorubicin agents on MDSC reduction in 4T1 breast cancer murine model were evaluated. Methods: 5ax105 of 4T1 tumor cells were injected into mammary fat pad of BALB/c female mice. Tumor bearing mice were randomly divided into 4 groups: PBS receiving control group, doxorubicin receiving groups at doses of 2.5 and 5 mg/kg, and 5-FU receiving group at dose of 50 mg/kg. Doxorubicin and 5-FU agents were intraperitoneally administrated at three doses with 5-day intervals and five doses for three times a week, respectively. Then, on day 20 post tumor cells injection, spleens and tumors were isolated to determine frequency of CD11b+ Gr1+ MDSCs by flow cytometry analysis. Results: 5-FU was able to reduce significantly both splenic and interatumoral MDSCs comparing to control group (p=0.0276 and p=0.0067, respectively). Also, Doxorubicin treatment at dose of 50 mg/kg was associated to a significant reduction of splenic MDSCs in comparison to untreated group (p=0.0382). However, only 5-FU injection led to inhibit notably tumor growth in comparison to control group (p=0.0139). Conclusion: Findings show that 5-FU has inhibitory effects on MDSCs and tumor growth in 4T1 tumor model. So, more investigations are needed to study combination of 5-FU with immune based approaches to enhance the efficacy of cancer therapies. [ABSTRACT FROM AUTHOR]

Diagnostic reasoning relies on cognitive heuristics to recognise patterns of symptoms and signs in order to arrive at a diagnosis. These rules of thumb allow us to rapidly diagnose common conditions that present in typical ways. However, they may lead us astray when common conditions present atypically or when a patient has a rare condition or multiple conditions causing their constellation of symptoms, signs, and test results, rather than having a single diagnosis to explain them all. This article describes strategies to help counteract diagnostic pitfalls, to expand diagnostic possibilities and to make diagnostic progress with complex, multielement cases. [ABSTRACT FROM AUTHOR]

Aim: To explore perceptions of annual surveillance with magnetic resonance imaging and perceptions of care during the examination among women with a hereditary risk of breast cancer. Design: Phenomenography. Methods: Fourteen face‐to‐face interviews using a semi‐structured interview guide were conducted among women undergoing surveillance in the southern region of Sweden. A seven‐step phenomenographic analysis with investigator triangulation was performed. Results: 'Considering own risk of developing breast cancer', 'Entrusting oneself to surveillance' and 'Living in a cycle' represented descriptive categories of perceptions. Family narratives introduced comprehension of own risk of breast cancer, followed by appraisal of own benefits of participating in surveillance. Entrusting oneself to surveillance included handing over management of diagnostic examinations and dealing with practical issues and diverse emotions related to surveillance. Planning life based around surveillance, struggling with fluctuating emotions, also between the examinations and questioning own identity implied the perception of living in a cycle. Conclusion: Surveillance for hereditary breast cancer implies living in a cycle of dealing with fluctuating emotions and planning life based around surveillance. Comprehension of one's own risk for breast cancer arises from awareness in the family. Women value the surveillance programme and trust the healthcare system. Implication for the Profession and Patient Care: Knowledge of women's perceptions of the surveillance programme and care is vital for supporting women in their decision‐making on attendance and providing person‐centred care during surveillance. Impact: A gap in explorative studies from the perspective of the individual woman in the context of surveillance for breast cancer and care in magnetic resonance imaging in surveillance was addressed. 'Considering own risk of developing breast cancer', 'Entrusting oneself to surveillance' and 'Living in a cycle' represented women's perceptions of surveillance and care. The study results have implications for person‐centred care among women in the surveillance programme. Patient or Public Contribution: No patient or public contribution. [ABSTRACT FROM AUTHOR]

Background: In this study, we wanted to evaluate the performance of sonomammography in distinguishing between benign and malignant breast cancers and to confirm the findings through histology. An attempt was made to diagnose and categorize the lesions using BI-RADS terminology in ultrasonography. Methods: This was a hospital based prospective study conducted among 100 female patients with symptoms affecting the breast who underwent sonomammographic imaging, at Shri B.M Patil Medical College, Hospital and Research Centre, over a period of 2 years from September 2022 to April 2024, after obtaining clearance from institutional ethics committee and written informed consent from the study participants. Results: 100 patients were selected for analysis, presenting with 118 masses. Out of them, 36 patients had malignancy, and 82 were benign. USG successfully differentiated between benign and malignant masses when the BI-RADS lexicon was incorporated with a sensitivity of 100% and a specificity of 97.56% for malignant masses. Conclusion: Good sensitivity and specificity are demonstrated by sonomammography(SMG) in identifying all breast lesions. As such, it may be deemed a more appropriate method of inquiry than mammography. For individuals under 40 years of age, it can serve as the primary screening method for breast lumps. Breast lesions can be better understood and managed with the help of BI-RADS classification. The diagnostic accuracy of SMG can be further improved by combining it with complementary imaging modalities. Multimodality approach is more sensitive than any single modality alone. Unnecessary interventions can be avoided in unequivocally benign lesions on SMG. USG can be used as a good screening test for the detection and differentiation of benign and malignant masses. Hence, it helps in early detection, early treatment and favorable outcome. [ABSTRACT FROM AUTHOR]

Introduction: FNAC has a pivotal role in the evaluation of breast lesions. Cytological grading systems are being utilized for the categorization of breast lesions. Modified Masood’s scoring System (MMSS) is used to improve the grading system for accurate pre-operative diagnosis. This study aims to assess the effectiveness and accuracy of the Modified Masood Scoring System for evaluating breast lesions and their correlation with histopathological diagnosis. Materials and Methods: This is a prospective study conducted in the Department of Pathology, MGM Medical College, Navi Mumbai which included 40 patients who presented with clinically palpable breast lump and were subjected to FNAC along with histopathological examination. The cytological smears were grouped into four categories according to MMSS. Correlation and concordance analysis between cytological categories and histopathological diagnosis was carried out. Observations and Results: The age of the patients ranged from 17 to 70 years with a mean age of 38.12 years, right-sided breast lesions were more common as compared to the left side. Of the total 40 cases, 27 cases were benign, and 13 cases were malignant on histopathology. The most common benign breast lesion was Fibroadenoma [Figure 1] and the malignant lesion was infiltrating duct carcinoma [Figure 2]. The sensitivity, specificity, Positive predictive value, Negative predictive value, and diagnostic accuracy were 76.9%, 100%, 100%, 90%, and 92.5% respectively. Conclusion: MMSS is simple, cost-effective, easily reproducible, reliable, and can be applied to FNAC aspirates to increase the diagnostic accuracy of Breast Lesions. [ABSTRACT FROM AUTHOR]

Some patients develop breast/chest lymphoedema following breast cancer treatment. Historically this group of patients has been managed in the same way as those with limb lymphoedema, through the application of compression in the form of vests or bras. Some patients reported pain and the feeling of being in a 'strait jacket' and, therefore, abandoned these items for lighter and more comfortable garments without any adverse effects. Reflecting on this insight, the author adapted breast/chest lymphoedema management by suggesting a change to lighter garments to patients who reported improved comfort, with no obvious negative impact on their lymphoedema. Within this article, the author gives a brief explanation of lymphatic mechanisms and factors relating to lymphoedema including signs and symptoms of breast oedema. There will be an exploration of the available treatments for lymphoedema along with treatment plans found to be effective by the author. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is known to have the worst outcome compared to the other forms of breast cancer. Moreover, molecular markers identified basal-like breast cancer (BLBC) phenotypes to be also related to a worse prognosis. In this study, we evaluated by immunohistochemistry (IHC) the prognostic significance of combining Cytokeratin-19 (CK19), E-cadherin, and Ki-67 tissue expression in triple-negative breast cancer (TNBC) cases presenting a basal-like (BLBC) or a non-basal-like (n-BLBC) phenotype to improve the selection and the monitoring of BC patients with a more aggressive outcome. Herein, when compared to n-BLBC, patients with BLBC showed a positive correlation with lymph node metastasis occurrence and lower survival rates. Immunohistochemistry analysis revealed significantly lower E-cadherin prevalence and higher prevalence of both CK19 and Ki-67 in BLBC when compared to n-BLBC. Spearman correlation showed that E-cadherin is negatively and significantly correlated to CK19 and Ki-67 expressions. Moreover, in BLBC, expressing both CK19 and Ki-67 combined with E-cadherin loss was associated with the worst relapse-free and overall survival. In conclusion, TNBC/BLBC phenotypes simultaneously losing E-cadherin and overexpressing CK19 and Ki-67 markers are the most aggressive forms. This combined analysis could be a predictive marker of poor prognosis. [ABSTRACT FROM AUTHOR]

Breast cancer with increased risk in women is identified with Breast Magnetic Resonance Imaging (Breast MRI) and this helps in evaluating treatment therapies. Breast MRI is time time-consuming process that involves the assessment of current imaging. This research work depends on the detection of breast cancer at the earlier stages. Among various cancers, breast cancer in women occurs in larger accounts for almost 30% of estimated cancer cases. In this research, many steps are followed for breast cancer detection like pre-processing, segmentation, augmentation, extraction of features, and cancer detection. Here, the median filter is utilized for pre-processing, as well as segmentation is followed after pre-processing, which is done by Psi-Net. Moreover, the process of augmentation like shearing, translation, and cropping are followed after segmentation. Also, the segmented image tends to process feature extraction, where features like shape features, Completed Local Binary Pattern (CLBP), Pyramid Histogram of Oriented Gradients (PHOG), and statistical features are extracted. Finally, breast cancer is detected using the DL model, SqueezeNet. Here, the newly devised Flamingo Search SailFish Optimizer (FSSFO) is used in training Psi-Net as well as SqueezeNet. Furthermore, FSSFO is the combination of both the Flamingo Search Algorithm (FSA) and SailFish Optimizer (SFO). [ABSTRACT FROM AUTHOR]

Objectives: Several studies have indicated that dietary interventions may offer protection against the development of cardiac damage in the case of anthracycline-induced cardiomyopathy (AIC). The goal of this study was to assess whether an evidence-based cardioprotective diet can be effective in preventing AIC in patients with breast cancer. Design: Randomized, open-label, controlled trial. The study period was set for 18 weeks, and the data were analyzed by generalized estimating equation modeling and one-way repeated measures analysis of variance. Setting/Location: Shahid Rajaie Hospital affiliated (Tehran, Iran). Subjects: Fifty anthracycline-treated patients with breast cancer. Interventions: Patients were randomized to receive either a 2-hour training in evidence-based cardio-protective diet or Carvedilol 6.25 mg bid. Outcome Measures: The primary outcome was the number of patients with abnormal left ventricular ejection fraction (LVEF) after 18 weeks. Results: At week 18, 12 (48%) out of 25 participants in the cardioprotective diet group had abnormal LVEF in comparison with 21 (84%) out of 25 in the carvedilol group (p = 0.007). Also, 2 (8%) out of 25 in the cardioprotective diet group compared with 7 (28%) out of 25 participants in the carvedilol group had abnormal global longitudinal strain (p = 0.066). The diet group showed significant improvements in the quality-of-life dimensions named "health change" and "general health" compared with the carvedilol group using the Short Form-36 Health Survey questionnaire. Conclusions: This study suggests that an evidence-based cardioprotective diet can contribute to the prevention of AIC. Although current treatments for AIC can be effective, further research is mandatory for more options. [ABSTRACT FROM AUTHOR]

Breast cancer is a potentially life-threatening disease is one of the most common cancers specially for women. For fast and effective treatment early detection of the tumor is very important. But the frequent checkup is not possible for many people with the traditional way of detection due to their cost and availability. To detect the biomedical imaging terahertz (THz) frequency is a suitable range and using patch antenna in biomedical detection is cost effective compared to the traditional methods. So, to detect the early stage of breast tumor, this article has proposed a graphene based THz antenna. The primary goal of this antenna is to detect the breast tumor with the improvement of the performance and the secondary goal is to make the antenna very light weighted. The design of the antenna was done using computer simulation technology (CST) studio and the dimension of the antenna is kept 18×23 μm2 and a breast phantom model has been designed and the performance analysis of the antenna has been done for both free space and breast tissue. The return loss of the antenna in free space is -52.4422 dB at 6.96 THz. The details of the detection of tumor through the proposed patch antenna has been shown in this study. [ABSTRACT FROM AUTHOR]

Background/Objectives: Heterodimer peptides targeting more than one receptor can be advantageous, as tumors can simultaneously express more than one receptor type. For human breast cancer, a promising biological target is tumor angiogenesis through αvβ3 integrin expression. Another promising target is Neuropeptide Y receptors, considering Y1R is overexpressed in 90% of human breast tumors. This article details the development and preclinical evaluation, both in vitro and in vivo, of a novel heterodimer peptide dual-receptor-targeting probe, [99mTc]HYNIC-cRGDfk-NPY, designed for imaging breast tumors. Methods: Female BALB/c healthy mice were used to perform biodistrubution studies and female SCID mice were subcutaneously injected with MCF-7 and MDA-MB-231 tumor cells. [99mTc]HYNIC-cRGDfk-NPY was intravenously administered to the mice, followed by ex vivo biodistribution studies and small-animal SPECT/CT imaging. Nonspecific tracer uptake in both models was determined by coinjecting an excess of unlabeled HYNIC-cRGDfk-NPY (100 µg) along with the radiolabeled tracer. Results: Imaging and biodistribution data demonstrate good uptake to estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) tumor models. The in vivo tumor uptakes of radiolabeled conjugate were 9.30 ± 3.25% and 4.93 ± 1.01% for MCF-7 and MDA-MB231, respectively. The tumor/muscle ratios were 5.65 ± 0.94 for the MCF-7 model and 7.78 ± 3.20 for MDA-MB231. Conclusions: [99mTc]HYNIC-cRGDfk-NPY demonstrated rapid blood clearance, renal excretion, and in vivo tumor uptake, highlighting its potential as a tumor imaging agent. [ABSTRACT FROM AUTHOR]

Background: The targeted therapy using breast cancer (BC)-associated biomarkers has significantly minimized the side-effects of BC treatment. This study aims to elucidate the role of Nectin2, NUF2, and Nectin4 gene expression in the pathogenesis of BC. Method: In this case-control study, the expression of Nectin2, Nectin4, and NUF2 genes was investigated through real-time polymerase chain reaction assay in 46 tumor tissues from BC patients and 46 adjacent non-tumorous tissues as a control group. Data were analyzed using SPSS-21 software, employing independent t-tests and oneway ANOVA. A P-value of <0.05 was considered statistically significant. Results: The results demonstrated a significant increase in the expression of the NUF2 gene in tumor tissues compared with adjacent normal tissues (P = 0.005, fold change = 3.7). No statistically significant difference was observed in the expression of Nectin2 and Nectin4 between the tumor and adjacent tissues. However, higher expression of Nectin2 was noted in the early stages of the disease, particularly in subtypes with estrogen receptor-positive (ER+), progesterone receptor positive (PR+), and human epidermal growth factor receptor 2 negative (HER2-). Furthermore, the expression of NUF2 and Nectin4 was elevated in advanced stages and triple-negative BC subtypes. Notably, the expression of these three genes was higher in patients aged ≤ 45 years. Conclusion: The findings suggest that the expression levels of NUF2, Nectin2, and Nectin4 genes may influence the initiation, progression, and pathogenesis of BC subtypes. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a heterogeneous disease characterized by significant global mortality and incidence rates. Annually, approximately 1 million cases of BC are diagnosed worldwide, with over 170,000 classified as triple-negative. Triple-negative breast cancer (TNBC) is a particularly aggressive subtype lacking targeted therapeutic options, which contributes to poorer outcomes compared to other BC subtypes. The five-year survival rate for patients with TNBC is roughly 30% lower than that for patients with other subtypes. TNBC treatment options are limited to surgery, radiotherapy, and chemotherapy. There is a critical need for the development of targeted therapies. Enhancing early detection through effective diagnostic and prognostic biomarkers can significantly improve survival rates. This review explores recent advancements in clinically relevant proteomic, genetic, and metabolomic biomarkers for TNBC, highlighting their potential roles as prognostic, diagnostic, and predictive markers that could facilitate personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Background: In India, breast carcinoma is the 2nd most common malignancy in women. Incidence increases every year which ranges approximately 20-32%. Incidence of breast cancer shows "AGE SHIFT" over the past twenty years in India that is incidence increased from 6 to 17% in the age group of 30-40 years. The 'Modified Triple Test' utilizes-Physical Examination, Ultrasonography of the breast as the radiological method, and FNAC for the diagnosis of palpable breast lumps. It is gaining acceptance with the recent advances in technology and refinements in the interpretative criteria of sonographically characterized masses. Methods A prospective cross sectional study of 50 female patients attending the out patient department of General Surgery, K.R. Hospital, Mysore, between March 2022 to January 2024, with the complaint of a palpable lump/lumps in the breast was undertaken. Results Most commonly affected age group being 30-39 years. Incidence increased from 7 to 16% between the age group of 30 and 40 years. The calculated P - value for parity study is 0.017 and it is shown that malignancy is common among nulliparous. For the menstrual status, the calculated p-value is 0.044 is significant. The breast tumor is common at left side account for about overall 54% age. Fibroadenoma is the most common benign tumor. It was inferred from the study that clinical examination has a sensitivity of 87.5% which means that around 12.5% of the breast carcinoma cases are missed clinically. Results of Modified Triple Test were Sensitivity: 100%, Specificity: 97.37%, PPV: 91.67%, NPV: 100%. Hence the modified triple test can be used as a reliable and fairly accurate means of diagnosis of breast carcinoma. Conclusion Our results show that the diagnostic accuracy of physical examination breast USG and FNA/CNB combined is comparable to that of histological examination. Ultrasound replacing mammography serve as an effective imaging modality in palpable breast lumps and is also more comprehensive. CNB is a suitable alternative when FNA is inconclusive, also offers additional information. Thus the use of MTT to complement findings in differential diagnosis of a lesion in a symptomatic women seeking medical care deserves acceptance and further evalution. [ABSTRACT FROM AUTHOR]

This paper presents a prototype of a portable and modular electrical impedance tomography (EIT) system for breast tumor detection. The proposed system uses MATLAB to generate three-dimensional representations of breast tissue. The modular architecture of the system allows for flexible customization and scalability. It consists of several interconnected modules. Each module can be easily replaced or upgraded, facilitating system maintenance and future enhancements. Testing of the prototype has shown promising results in preliminary screening based on experimental studies. Agar models were used for the experimental stage of this project. The 3D representations provide clinicians with valuable information for accurate diagnosis and treatment planning. Further research and refinement of the system is warranted to validate its performance in future clinical trials. [ABSTRACT FROM AUTHOR]

Polygenic risk scores (PRSs) are rapidly emerging as a way to measure disease risk by aggregating multiple genetic variants. Understanding the interplay of the PRS with environmental factors is critical for interpreting and applying PRSs in a wide variety of settings. We develop an efficient method for simultaneously modeling gene-environment correlations and interactions using the PRS in case-control studies. We use a logistic-normal regression modeling framework to specify the disease risk and PRS distribution in the underlying population and propose joint inference across the 2 models using the retrospective likelihood of the case-control data. Extensive simulation studies demonstrate the flexibility of the method in trading-off bias and efficiency for the estimation of various model parameters compared with standard logistic regression or a case-only analysis for gene-environment interactions, or a control-only analysis, for gene-environment correlations. Finally, using simulated case-control data sets within the UK Biobank study, we demonstrate the power of our method for its ability to recover results from the full prospective cohort for the detection of an interaction between long-term oral contraceptive use and the PRS on the risk of breast cancer. This method is computationally efficient and implemented in a user-friendly R package. [ABSTRACT FROM AUTHOR]

Background/Objectives: Trefoil factor 1 (TFF1) plays a role in the mucus barrier. Methods: To evaluate the prevalence of TFF1 expression in cancer, a tissue microarray containing 18,878 samples from 149 tumor types and 608 samples of 76 normal tissue types was analyzed through immunohistochemistry (IHC). Results: TFF1 staining was detectable in 65 of 149 tumor categories. The highest rates of TFF1 positivity were found in mucinous ovarian carcinomas (76.2%), colorectal adenomas and adenocarcinomas (47.1–75%), breast neoplasms (up to 72.9%), bilio-pancreatic adenocarcinomas (42.1–62.5%), gastro-esophageal adenocarcinomas (40.4–50.0%), neuroendocrine neoplasms (up to 45.5%), cervical adenocarcinomas (39.1%), and urothelial neoplasms (up to 24.3%). High TFF1 expression was related to a low grade of malignancy in non-invasive urothelial carcinomas of the bladder (p = 0.0225), low grade of malignancy (p = 0.0003), estrogen and progesterone receptor expression (p < 0.0001), non-triple negativity (p = 0.0005) in invasive breast cancer of no special type, and right-sided tumor location (p = 0.0021) in colorectal adenocarcinomas. Conclusions: TFF1 IHC has only limited utility for the discrimination of different tumor entities given its expression in many tumor entities. The link between TFF1 expression and parameters of malignancy argues for a relevant biological role of TFF1 in cancer. TFF1 may represent a suitable therapeutic target due to its expression in only a few normal cell types. [ABSTRACT FROM AUTHOR]

Simple Summary: Research continues to show that exercising at recommended levels is associated with lower mortality rates and decreased risk of recurrence in breast cancer survivors (BCS). Moreover, those BCS exercising at levels meeting guidelines have higher self-reported health-related quality of life (HR-QOL) than those that do not. This includes lowered levels of perceived global stress. However, which modalities of exercise are most effective has yet to be determined. Our study investigates changes in stress experienced by breast cancer survivors participating in one of three different exercise modalities conducted over six months, as indicated by self-report and salivary cortisol measures. The revealed improvement in constructs of Health Related-Quality of Life (HR-QOL) suggest that engagement in exercise had a greater impact on outcomes than any particular modality. Background/Objectives: Extensive evidence suggests that exercise is physically and mentally beneficial for cancer survivors. This study reports on changes in self-reported stress, physiological biomarkers for stress (salivary cortisol), and HR-QOL constructs for fifty breast cancer survivors participating in one of three different exercise programs over 6 months. Methods: Fifty post-treatment breast cancer survivors were randomized to either therapeutic yoga-based exercise (YE), comprehensive exercise (CE) (aerobic, resistance, flexibility), or choosing (C) their own exercise activities. Participants completed the Perceived Stress Scale (PSS), Medical Outcomes Short-Form 36® (SF-36), and the Pittsburgh Sleep Quality Index (PSQI). Five samples of salivary cortisol were collected on two consecutive days. The 10 samples were used to calculate the diurnal rhythm slope. Outcome measures were repeated after six months. Results: All groups improved in HR-QOL measures of PSS; PSQI sleep quality components of latency and daytime functioning; and five of the ten SF-36 scales (Mental Component Scale, Social Functioning subscale, Mental Health subscale, Physical Component Scale, Physical Functioning subscale). Although the CE group observed the most favorable change in cortisol (−0.183), where cortisol slope changes approached significance (p = 0.057), but no significant decrease in cortisol between groups were noted. Conclusions: Our results suggest that it is the engagement of, rather than the specific type of exercise, which is associated with improved HR-QOL. However, longer-term studies with better adherence monitoring and larger sample sizes are needed to better determine clinical impact. [ABSTRACT FROM AUTHOR]

Simple Summary: Exogenous ketone esters (KEs) are compounds that elevate blood ketones without dietary restriction and they show promise as anti-cancer agents. This study examined the effects of an exogenous ketone ester-supplemented (eKET) diet in mouse models of metastatic breast and kidney cancers. Our eKET diet slowed tumor growth and reduced metastatic spread to the lungs in both cancer types. The mechanisms behind these effects differed: the eKET diet downregulated genes involved in Wnt and TGFβ signaling in mammary cancers, whereas it downregulated genes related to hypoxia and DNA damage repair in tumor-bearing kidneys. The diet was safe for use overall but was associated with some negative physiological effects in mice with renal cancer. Thus, eKET diets could be an effective addition to current cancer treatments, but additional work is needed to fully understand their limitations. Background/Objectives: Ketone esters (KEs) exhibit promise as anti-cancer agents but their impact on spontaneous metastases remains poorly understood. Although consumption of a ketogenic diet (KD) that is low in carbohydrates and high in fats can lead to KE production in vivo, the restrictive composition of KDs may diminish adherence in cancer patients. Methods: We investigated the effects of an exogenous ketone ester-supplemented (eKET), carbohydrate-replete diet on tumor growth, metastasis, and underlying mechanisms in orthotopic models of metastatic breast (4T1-Luc) and renal (Renca-Luc) carcinomas. Mice were randomized to diet after tumor challenge. Results: Administration of KEs did not alter tumor cell growth in vitro. However, in mice, our eKET diet increased circulating β-hydroxybutyrate and inhibited primary tumor growth and lung metastasis in both models. Body composition analysis illustrated the overall safety of eKET diet use, although it was associated with a loss of fat mass in mice with renal tumors. Immunogenetic profiling revealed divergent intratumoral eKET-related changes by tumor type. In mammary tumors, Wnt and TGFβ pathways were downregulated, whereas in renal tumors, genes related to hypoxia and DNA damage repair were downregulated. Conclusions: Thus, our eKET diet exerts potent antitumor and antimetastatic effects in both breast and renal cancer models, albeit with different modes of action and physiologic effects. Its potential as an adjuvant dietary approach for patients with diverse cancer types should be explored further. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the real-world efficacy and safety of combining pembrolizumab, a novel immunotherapy agent, with chemotherapy in early-stage triple-negative breast cancer treatment. We specifically aimed to validate clinical trial results in routine practice. A total of 108 Turkish patients receiving neoadjuvant therapy were examined. The combined regimen demonstrated high efficacy, with 64% of patients achieving pathological complete response, and exhibited generally favorable safety profiles with predominantly mild adverse events. These findings support the use of this combination as a standard treatment for this aggressive breast cancer subtype. However, the results underscore the need for further research to identify optimal patient selection criteria, which can inform oncologists' decision-making and potentially enhance outcomes for patients with triple-negative breast cancer. Background/Objectives: Following the results of the phase 3 KEYNOTE-522 trial, the U.S. Food and Drug Administration approved pembrolizumab, a humanized IgG4 kappa monoclonal antibody, in combination with neoadjuvant chemotherapy as a new standard of care for high-risk early-stage triple-negative breast cancer (TNBC). This retrospective, multicenter study in Türkiye assessed the real-world efficacy and safety of neoadjuvant pembrolizumab combined with chemotherapy in early-stage TNBC. Methods: The study included 108 patients treated between 2021 and 2023 across 14 oncology centers. Three distinct neoadjuvant regimens incorporating pembrolizumab were administered at the discretion of the treating physicians. The primary outcomes were the pathological complete response (pCR) rate after neoadjuvant therapy and the 2-year event-free survival (EFS) and overall survival (OS) rates. Results: The observed pCR rate was 63.9%, closely mirroring the 64.8% reported in the KEYNOTE-522 trial. At the two-year mark, the EFS rate was 87.2% and the OS rate was 92.3%. Multivariable analysis identified pCR as the sole independent predictor of both EFS and OS. The safety profile was consistent with previous clinical trial data, with most adverse events being of grade 1–2 in severity. Conclusions: These findings provide valuable real-world confirmation of the efficacy and safety of neoadjuvant pembrolizumab–chemotherapy in early-stage TNBC, complementing evidence from randomized trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Idiopathic granulomatous mastitis (IGM) is a rare breast disease that can be mistaken for inflammatory breast cancer. It requires a tissue biopsy for an accurate diagnosis. Even though it is not cancerous, IGM can cause emotional distress because of severe pain and ensuing breast deformity. It is important to distinguish IGM from other breast inflammations caused by infections. IGM is mostly found in premenopausal women, often after pregnancy or breastfeeding. Smoking and contraceptive use might be risk factors, but the evidence is unclear. The treatment options include NSAIDs, steroids, immunosuppressants, surgery, prolactin suppressants, and antibiotics; many patients relapse, making treatment challenging. This review summarizes current information, which mostly comes from case reports and small studies, and presents GRAMAREG as a registry for IGM initiated by the EUBREAST Study Group, which aims to collect detailed data on IGM to improve the knowledge base for diagnosis and treatment. Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast condition often mistaken for inflammatory breast cancer and, therefore, requires a biopsy for accurate diagnosis. Although not cancerous, IGM can cause emotional distress because of severe pain and ensuing breast deformity. Differentiating IGM from other breast inflammations caused by infections is essential. IGM mostly affects premenopausal women and is potentially associated with recent pregnancies and breastfeeding. The risk factors, including smoking and contraceptive use, have inconsistent associations. Steroid responses suggest an autoimmune component, though specific markers are lacking. Methods: We performed a narrative review on potential risk factors, diagnostics, and therapy of IGM. Results: Diagnostics and clinical management of IGM are challenging. The treatment options include NSAIDs, steroids, surgery, antibiotics, immunosuppressants, prolactin suppressants, and observation, each with varying effectiveness and side effects. Conclusions: Current IGM treatment evidence is limited, based on case reports and small series. There is no consensus on the optimal management strategy for this disease. The GRAMAREG study by the EUBREAST Study Group aims to collect comprehensive data on IGM to improve diagnostic and treatment guidelines. By enrolling patients with confirmed IGM, the study seeks to develop evidence-based recommendations, enhancing patient care and understanding of this condition. [ABSTRACT FROM AUTHOR]

Simple Summary: Limited knowledge exists on the effects of the COVID-19 pandemic and the pandemic lockdown on cancer detection and diagnoses in Switzerland. Population-based Swiss cantonal cancer registry data of the cantons of Zurich and Zug from 2018/19 to 2021 were used. Differences in cancer diagnoses were analyzed descriptively and using multivariate regression models. A decrease in all-cancer incidence was observed in 2020 compared to 2018/19, mainly during the lockdown phase in April. Meanwhile, higher all-cancer incidence rates were observed in 2021 compared to 2018/19. The impact in Switzerland was less severe than in other countries. Our findings may inform the decisions of policymakers and the public health system during future pandemics. Background/Objectives: This study aims to investigate differences in cancer diagnosis based on absolute case numbers and age-standardized incidence rate ratios (IRRs) in the pre-Coronavirus disease 2019 (COVID-19) years (2018/19) and the first two years of the COVID-19 pandemic (2020, 2021) in two Swiss cantons. Methods: Data of the Swiss cantonal cancer registry of the cantons of Zurich (ZH) and Zug (ZG) were used to descriptively investigate differences in annual and monthly absolute numbers regarding all-cancer and the five most common cancer types. Directly age-standardized monthly incidence rates (IRs) were calculated. Multivariate Quasipoisson regression models were fitted to determine the IRRs with 95% confidence intervals (95% CI). Results: Annual absolute numbers of all investigated cancers were similar in 2018/19, 2020, and 2021, except for prostate cancer (increase of 20.8% in 2021 compared to 2018/19). In 2020, there were generally more cancer diagnoses in January and February followed by a decrease in April and May. Compared to the pre-COVID-19 period, lower IRs were observed in 2020 for all-cancer (IRR = 0.96 [95% CI 0.96, 0.97]) and female breast cancer (0.92 [0.89, 0.96]), whereas higher IRs were observed in 2021 for all-cancer (1.02 [1.02, 1.02]) and prostate cancer (1.23 [1.18, 1.28]). Conclusions: Cancer detection and diagnoses decreased during the first year of the pandemic, especially during the most stringent lockdown phase in April. The findings of this study may inform the decisions of policymakers and public health system during future pandemics. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is diagnosed in 2.3 million women each year and kills 685,000 (~30% of patients) worldwide. The most dangerous breast cancer is triple-negative breast cancer (TNBC). TNBC is very diverse, with 12 underlying subtypes. This great deal of patient diversity, along with the lack of broad-application targetable mechanistic markers (such as ER, PR, and HER2, which are present in other breast cancer subtypes but missing in TNBC), gives TNBC patients the worst outcomes of any breast cancer type. We aim to remedy this by exploring the molecular mechanisms across TNBC samples and subtypes. Molecular mechanisms are potentially targetable for treatment. We explore these options as part of our RNA-sequencing analysis. Our novel findings include highly accurate mechanistic markers identified using machine learning methods, including CIDEC (97.1% accuracy alone). Additionally, we found TNBC subtype-differentiating mechanistic markers, including PDE3B, CFD, IFNG, and ADM, which are targets with known therapeutics and potential for drug repurposing. Background/Objectives: Breast cancer is diagnosed in 2.3 million women each year and kills 685,000 (~30% of patients) worldwide. The prognosis for many breast cancer subtypes has improved due to treatments targeting the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). In contrast, patients with triple-negative breast cancer (TNBC) tumors, which lack all three commonly targeted membrane markers, more frequently relapse and have lower survival rates due to a lack of tumor-selective TNBC treatments. We aim to investigate TNBC mechanistic markers that could be targeted for treatment. Methods: We performed a secondary TNBC analysis of 196 samples across 10 publicly available bulk RNA-sequencing studies to better understand the molecular mechanism(s) of disease and predict robust mechanistic markers that could be used to improve the mechanistic understanding of and diagnostic capabilities for TNBC. Results: Our analysis identified ~12,500 significant differentially expressed genes (FDR-adjusted p-value < 0.05), including KIF14 and ELMOD3, and two significantly modulated pathways. Additionally, our novel findings include highly accurate mechanistic markers identified using machine learning methods, including CIDEC (97.1% accuracy alone), CD300LG, ASPM, and RGS1 (98.9% combined accuracy), as well as TNBC subtype-differentiating mechanistic markers, including the targets PDE3B, CFD, IFNG, and ADM, which have associated therapeutics that can potentially be repurposed to improve treatment options. We then experimentally and computationally validated a subset of these findings. Conclusions: The results of our analyses can be used to better understand the mechanism(s) of disease and contribute to the development of improved diagnostics and/or treatments for TNBC. [ABSTRACT FROM AUTHOR]