Search Results (656)

Breast cancer remains a major global health challenge, with treatment access further constrained during the COVID-19 pandemic, particularly in resource-limited settings. This study evaluates the in vitro effects of hypofractionated versus conventionally fractionated radiotherapy on three breast cell lines: MCF-7 (oestrogen receptor-positive, ER⁺/PR⁺), MDA-MB-231 (triple-negative: ER⁻/PR⁻/HER2⁻), and MCF-10A (non-tumorigenic mammary epithelial). Cells were exposed to cobalt-60 γ-rays, and radiobiological endpoints assessed included clonogenic survival, α/β ratios, adaptive responses, migration, invasion, and cytotoxicity through lactate dehydrogenase assays. The α/β ratios ranged from 2.5 to 5.4 Gy across breast cancer subtypes. Hypofractionation reduced survival in hormone receptor-positive cells, whereas triple-negative cells exhibited increased survival. Adaptive radiation responses enhanced viability across all cell lines, while non-cancerous MCF-10A cells demonstrated reduced migration following treatment. These findings suggest that hypofractionated radiotherapy may be beneficial in hormone receptor-positive breast cancer, while triple-negative disease may show a trend toward different responses, although this was not statistically significant (MDA-MB-231, p = 0.290). The results underscore the importance of tailoring fractionation strategies to breast cancer subtype and highlight the translational potential of preclinical radiobiology in guiding personalised radiation oncology approaches. Full article

Background/Objectives: Male breast cancer (MBC) is rare, accounting for less than 1% of all breast cancers. Given its low incidence, male breast cancer (MBC) remains understudied; this 33-year Serbian cohort was assessed for clinicopathological features, therapeutic approaches, genetic alterations, and survival. Methods: We retrospectively analyzed MBC patients diagnosed between 1991 and 2024 at the Institute for Oncology and Radiology of Serbia. Data included demographics, tumor characteristics, and stage, treatment, hormone receptor and HER2 status, Ki-67 index, genetic testing, and survival. Results: A total of 191 patients were identified (median age 66). Family history was negative in 91% and positive in 5.8%. T2 tumors were most frequent (36%), and 96% presented without metastasis. Mastectomy with axillary or sentinel lymph node dissection was performed in 78.5%. Neoadjuvant chemotherapy and radiotherapy were administered in 5.8% and 8.4%. Estrogen receptor positivity was 72%, progesterone receptor 88%, HER2 overexpression 11.0%, and triple-negative tumors 2.6% (40% with axillary involvement). High Ki-67 (≥15%) was recorded in 28.8%. Adjuvant chemotherapy, radiotherapy, and hormone therapy were given in 36%, 58%, and 68%. Among 37 genetically tested patients, seven had pathogenic variants (BRCA1, BRCA2, CHEK2, PALB2). Disease recurrence occurred in 30%. Median follow-up was 53 months. Median disease-free survival (DFS) was 82 months (1-, 2-, 5-, 10-year DFS: 87%, 73%, 57%, 39%). Median overall survival (OS) 131 months (1-, 2-, 5-, 10-year OS: 95%, 93%, 73%, 53%). Conclusions: This long-term cohort highlights the predominance of hormone-receptor positivity, the infrequency of germline mutations, and moderate survival rates, informing patient management and guiding future studies. Full article

Purpose: With the addition of palbociclib to endocrine therapy, many hormone receptor-positive (HR+) metastatic breast cancer (mBC) patients experience toxicities that can lead to dose reductions and cycle delays. We examined the actual doses of palbociclib received by patients and their treatment responses. These dose adjustments, made at the physician’s discretion, are not always consistent with pharmaceutical company recommendations. The aim of this study was to assess the influence of dose adjustments on dose intensity and treatment response in our patients. Methods: Records of patients with HR+ mBC treated with palbociclib between December 2016 and January 2019 at the Sainte-Catherine Institute were retrospectively reviewed. Dose intensity was defined as the total dose of palbociclib received by each patient during the first six months of treatment. Anticipated dose reductions and extended cycle delays were recorded. Treatment response at six months and survival were assessed using statistical analyses. Results: A total of 131 women were included; the median age was 67 years. Forty-six patients (35%) experienced an anticipated dose reduction or an extended cycle delay during the first six months of treatment. Logistic regression analysis showed that factors correlated with six-month treatment response included anticipated dose reduction or extended cycle delay (OR = 14.6, 95% CI 3.74–97.4, p < 0.001), cycle delay > 4 weeks (OR = 5.94, 95% CI 1.58–21, p = 0.01), initial dosage < 125 mg (OR = 4.09, 95% CI 1.13–13.7, p = 0.034), and six-month dose intensity < 14,250 mg (OR = 26.0, 95% CI 4.91–481, p < 0.001). Conclusions: In this real-world assessment of clinical outcomes in French patients with HR+ mBC treated with palbociclib, a palbociclib dose intensity lower than recommended—particularly due to cycle delays longer than four weeks—was associated with an increased risk of six-month disease progression. Full article

Sustainable food production for a growing population requires farming practices that reduce chemical inputs while maintaining soil as a living, renewable foundation for productivity. This review synthesizes current advances in understanding how endophytic fungi (EFs) interact with the soil microbiome and contribute to the physicochemical and biological dimensions of soil health in arable ecosystems. We examine evidence showing that EFs enhance plant nutrition through phosphate solubilization, siderophore-mediated micronutrient acquisition, and improved nitrogen use efficiency while also modulating plant hormones and stress-responsive pathways. EFs further increase crop resilience to drought, salinity, and heat; suppress pathogens; and influence key soil properties including aggregation, organic matter turnover, and microbial network stability. Recent integration of multi-omics, metabolomics, and community-level analyses has shifted the field from descriptive surveys toward mechanistic insight, revealing how EFs regulate nutrient cycling and remodel rhizosphere communities toward disease-suppressive and nutrient-efficient states. A central contribution of this review is the linkage of EF-mediated plant functions with soil microbiome dynamics and soil structural processes framed within a translational pipeline encompassing strain selection, formulation, delivery, and field scale monitoring. We also highlight current challenges, including context-dependent performance, competition with native microbiota, and formulation and deployment constraints that limit consistent outcomes under field conditions. By bridging microbial ecology with agronomy, this review positions EFs as biocontrol agents, biofertilizers, and ecosystem engineers with strong potential for resilient, low-input, and climate-adaptive cropping systems. Full article

Background: HER2-low breast cancer (HER2 immunohistochemical [IHC] score 1+, or IHC 2+ without HER2 gene amplification) is distinct from HER2-positive and HER2-0 breast cancer (IHC 0), with a differing prognosis and specific therapeutic options. The DESTINY-Breast04 trial demonstrated notable efficacy of the HER2 antibody–drug conjugate trastuzumab deruxtecan over standard chemotherapy in patients with metastatic breast cancer (MBC) defined as HER2-low. More recently, the DESTINY-Breast06 trial confirmed this benefit in hormone receptor-positive and HER2-ultralow (less than 1+, but with ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining) cases, prompting re-evaluation of HER2 diagnostic thresholds and treatment strategies. Methods: Eligible patients were women with HER2-low or HER2-0 MBC evaluated at MD Anderson between January 2006 and January 2019. HER2-low was defined as either (1) IHC 1+ or (2) IHC 2+ and negative on fluorescence in situ hybridization. Multivariate logistic regression was used to evaluate distinct clinicopathologic features of patients with HER2-low status. Overall survival (OS) was estimated by the Kaplan–Meier method. Multivariate Cox proportional hazards regression was applied to assess the effects of covariates of interest on OS across different HER2 groups. Results: We included 3834 women: 2637 (69%) with recurrent and 1197 (31%) with de novo MBC; HER2-low disease was present in 1575 (60%) and 712 (59%), respectively. In de novo cases, higher nuclear grade was associated with HER2-low status (grade 2 vs. 1, OR = 2.02, p = 0.007; grade 3 vs. 1, OR = 1.87, p = 0.015), while recurrent cases were associated with ER-positivity (OR = 1.96, p < 0.001) and prior adjuvant radiotherapy (OR = 0.79, p = 0.007). Median OS was 3.2 years (95% CI 3.0–3.5). In de novo disease, Black race (HR = 1.48), metaplastic (HR = 3.15) or other non-ductal/lobular histologies (HR = 2.36), and grade 3 (HR = 1.67) predicted worse OS, whereas Hispanic ethnicity (HR = 0.74) and Other races (HR = 0.57), higher ER (HR = 0.48–0.41) and PR (HR = 0.72–0.53), and HER2-low status (HR = 0.77) conferred improved outcomes. In recurrent disease, Black race predicted worse OS (HR = 1.21, 95% CI 1.05–1.39), while Other race (HR = 0.78, 95% CI 0.62–0.97), higher ER (HR = 0.69–0.44) and PR (HR = 0.73–0.73), and HER2-low (HR = 0.89) were protective. HER2 discordance between primary and metastatic sites occurred in 38.8% of recurrent and 13.1% of de novo cases. Conclusions: HER2-low status was significantly associated with longer OS compared to HER2-0 status in both recurrent and de novo MBC cases. These real-world data help establish the prevalence of HER2-low status and its distinct outcomes. The discrepancy in HER2-low status between the primary tumor and metastatic sites highlights the potential for changes in HER2 expression over time, exploring the interaction between HER2-low breast cancer and the tumor microenvironment and emphasizing the importance of monitoring and reassessing HER2 status at various stages to guide treatment decisions effectively and the need for more quantitative and reproducible HER assays. Full article

Background/Objectives: Metabolism is fundamental to all living organisms. It comprises a highly complex network of fine-tuned chemical reactions that sustain life but also generate by-products that damage cellular biomolecules, including DNA, thereby contributing to aging and disease. As metabolism can be largely modified by dietary alterations, it has the potential to positively or negatively affect health and disease. Interestingly, many aging-associated illnesses known to be influenced by diet also show a causal relation with DNA damage. As DNA keeps all instructions for life, and DNA lesions, if unrepaired, interfere with vital processes such as DNA replication and transcription, DNA damage may be an important mediator of the impact of nutrition on health and aging. Methods: Here, we discuss the genome-protective effects of various oral interventions in mice, aiming to elucidate which nutritional alterations lower DNA damage and promote overall health. Results: Our analysis covers a wide range of interventions with reported positive impacts on genomic stability, including modified diets (e.g., dietary restriction, probiotics, micronutrients, fatty acids, and hormones), NAD+ precursors (e.g., nicotinamide riboside), plant derivatives, and synthetic drugs. Among these, caloric and dietary restriction emerge as the most potent, generic modulators of DNA damage and repair processes, enhancing aspects of repair efficiency through metabolic recalibration and improved cellular resilience. Other interventions, like NAD+ precursors, activate partly similar pathways without necessitating reduced food intake. Conclusions: While many interventions show promise, their effects are often less pronounced or are process-specific compared to caloric or dietary restriction. Additionally, many substances lack comprehensive exploration of their genome-protective effects in mice, with often only a small number of studies examining their impact on genome stability. Moreover, the heterogeneity between studies limits direct comparison. However, the observed overlap in mechanistic effects between treatments lends credibility to their potential efficacy. Ultimately, a deeper understanding of these mechanisms could pave the way for translating these findings into, e.g., combination treatments to promote healthy aging in humans. Full article

Obesity is among the top contributing factors for non-communicable chronic disease development and has attained menacing global proportions, affecting approximately one of eight adults. Phytochemicals that support energy metabolism and prevent obesity development have been the subject of intense research endeavors over the past several decades. Cycloastragenol is a natural triterpenoid compound and aglycon of astragaloside IV, known for activating telomerase and mitigating cellular aging. Here, we aim to characterize the effect of cycloastragenol on lipid metabolism in a glucose-induced obesity model in Caenorhabditis elegans. We assessed the changes in the body length, width, and area in C. elegans maintained under elevated glucose through automated WormLab system. Lipid accumulation in the presence of either cycloastragenol (100 μM) or orlistat (12 μM), used as a positive anti-obesity control drug, was quantified through Nile Red fluorescent staining. Furthermore, we evaluated the changes in key energy metabolism molecular players in GFP-reporter transgenic strains. Our results revealed that cycloastragenol treatment decreased mean body area and reduced lipid accumulation in the C. elegans glucose-induced model. The mechanistic data indicated that cycloastragenol suppresses the nuclear hormone receptor family member NHR-49 and the delta(9)-fatty-acid desaturase 7 (FAT-7) enzyme, and activates the 5′-AMP-activated protein kinase catalytic subunit alpha-2 (AAK-2) and the protein skinhead 1 (SKN-1) signaling. Collectively, our findings highlight that cycloastragenol reprograms lipid metabolism by down-regulating the insulin-like receptor (daf-2)/phosphatidylinositol 3-kinase (age-1)/NHR-49 signaling while simultaneously enhancing the activity of the AAK-2/NAD-dependent protein deacetylase (SIR-2.1) pathway. The anti-obesogenic potential of cycloastragenol rationalizes further validation in the context of metabolic diseases and obesity management. Full article

Background: Osteoporosis and osteopenia are prevalent bone diseases characterized by reduced bone mineral density (BMD) and an increased risk of fractures, particularly in postmenopausal women. While dual-energy X-ray absorptiometry (DXA) remains the gold standard for diagnosis, it has limitations regarding accessibility, cost, and predictive capacity for fracture risk. Machine learning (ML) approaches offer an opportunity to develop automated and more accurate diagnostic models by incorporating both BMD values and clinical variables. Method: This study retrospectively analyzed BMD data from 142 postmenopausal women, classified into 3 diagnostic groups: normal, osteopenia, and osteoporosis. Various supervised ML algorithms—including Support Vector Machines (SVM), k-Nearest Neighbors (k-NN), Decision Trees (DT), Naive Bayes (NB), Linear Discriminant Analysis (LDA), and Artificial Neural Networks (ANN)—were applied. Feature selection techniques such as ANOVA, CHI2, MRMR, and Kruskal–Wallis were used to enhance model performance, reduce dimensionality, and improve interpretability. Model performance was evaluated using 10-fold cross-validation based on accuracy, true positive rate (TPR), false negative rate (FNR), and AUC values. Results: Among all models and feature selection combinations, SVM with ANOVA-selected features achieved the highest classification accuracy (94.30%) and 100% TPR for the normal class. Feature sets based on traditional diagnostic regions (L1–L4, femoral neck, total femur) also showed high accuracy (up to 90.70%) but were generally outperformed by statistically selected features. CHI2 and MRMR methods also yielded robust results, particularly when paired with SVM and k-NN classifiers. The results highlight the effectiveness of combining statistical feature selection with ML to enhance diagnostic precision for osteoporosis and osteopenia. Conclusions: Machine learning algorithms, when integrated with data-driven feature selection strategies, provide a promising framework for automated classification of osteoporosis and osteopenia based on BMD data. ANOVA emerged as the most effective feature selection method, yielding superior accuracy across all classifiers. These findings support the integration of ML-based decision support tools into clinical workflows to facilitate early diagnosis and personalized treatment planning. Future studies should explore more diverse and larger datasets, incorporating genetic, lifestyle, and hormonal factors for further model enhancement. Full article

Background/Objectives: Breast cancer is a prevalent and heterogeneous disease with multiple subtypes, which are defined by characteristics such as molecular biomarkers and metastatic status. This study aimed to profile the metabolic activity of various breast cancer subtypes, both with and without chemotherapy (doxorubicin) application. Methods: Six human breast cell lines were evaluated, two non-tumorigenic controls and four cancerous lines. The cancer lines were clustered as primary-derived, metastasis-derived, triple-negative (TNBC), and strong hormone receptor-positive (ER+/PR+) and analyzed using the Biolog phenotype mammalian microarrays (PM-M1 to PM-M8) to assess metabolic activity via NADH production under a wide array of substrate parameters. Results: Unique metabolic profiles emerged across the subtypes and clusters; the TNBC and metastatic cells demonstrated enhanced utilization of glycolytic and anaerobic substrates consistent with the Warburg effect. The ER+/PR+ cells showed heightened glucose utilization and unique sensitivity to metabolic effectors and doxorubicin. Additionally, significant metabolic differences were observed in nucleoside and amino acid utilization between cancer and control cells, particularly in metastatic and TNBC lines. Conclusions: Our findings reveal the profound metabolic diversity among breast cancer subtypes and highlight distinct substrate dependencies for proliferation. The results additionally provide a framework for developing metabolic biomarkers and targeted therapies for chemotherapy resistance in breast cancer subtypes. Full article

Background/Objectives: Thyroid eye disease (TED) can lead to structural and microvascular changes in the orbit and retina. This study aimed to investigate the associations between Clinical Activity Score (CAS), orbital magnetic resonance imaging (MRI) measurements, and retinal microvascular changes in TED patients. Methods: This cross-sectional study included 38 patients (76 eyes) with TED. Each patient underwent a comprehensive ophthalmological evaluation, CAS assessment, and a detailed medical history. Optical coherence tomography angiography (OCTA) was performed to quantify vessel density (VD) in the superficial and deep capillary plexus (SCP and DCP). Exophthalmos, extraocular muscle thickness and orbital fat thickness were measured on MRI scans to evaluate structural changes. Laboratory analyses included thyroid hormone levels, thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase antibodies (anti-TPO), and lipid profile. Results: Active TED patients (CAS ≥ 3) had significantly higher TRAb levels (p < 0.001), while anti-TPO did not differ between groups. Active eyes showed significantly higher DCP VD in the whole image (p = 0.013), parafovea (p = 0.012), and perifovea (p = 0.009) across all quadrants, with no difference in SCP or the foveal avascular zone (FAZ). In linear mixed model regression analyses, after adjusting for previous glucocorticosteroid therapy, higher triglycerides, greater medial rectus thickness, and whole-image DCP VD independently predicted higher CAS values (R² = 42, p < 0.001). After adjusting for age and sex, CAS remained significantly positive predictor of DCP VD in the parafovea (R² = 0.22, p < 0.001). Conclusions: Changes in DCP VD reflect TED activity and structural orbital involvement. Full article

Background/Objectives: The assessment of endometriosis (EMS)-associated pain is important, but only very few studies address the potential use of questionnaires for non-invasive prediction of the disease. Methods: In a prospective observational study from 2016 to 2024 with patients (n = 228) using hormonal contraception, all women with suspected EMS answered two questionnaires and were examined physically and with transvaginal ultrasound (TVUS). If deep infiltrating EMS (DIE) was suspected, magnetic resonance imaging (MRI) was performed. EMS diagnosis was confirmed by histological examination. Statistical analysis was mainly performed using 2 × 2 contingency tables. The decision tree was created manually. Results: The mean numerical rating scales (NRSs) of EMS-positive compared to EMS-negative patients were ~4-fold higher (4.45 and 1.15, respectively). Patients with EMS have, significantly, ~3 times more significant parameters compared to patients without EMS (18.5 and 5.9, respectively). In combination with dysuria and lightning-like pain, this resulted in very good prediction. A decision tree yielded a sensitivity of 0.924, a specificity of 0.917, a positive predictive value (PPV) of 0.924, a negative predictive value (NPV) of 0.917, and a positive likelihood ratio of 11.2, indicating a very good diagnostic test. There is no typical endometriosis pain, but various pain patterns are predictive of EMS. Conclusions: Thus, a reliable non-invasive EMS diagnosis by questionnaires is possible and could reduce the delay in the detection of EMS. Full article

Background: Breast cancer remains the most common malignancy among women worldwide. Current systemic treatment strategies include chemotherapy, immunotherapy, bone-stabilizing agents, endocrine therapy for hormone receptor-positive disease, anti-HER2 therapy for HER2-positive disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA mutation cases. However, effectively overcoming drug resistance and reducing recurrence and metastasis rates remain major therapeutic challenges. Methods: To investigate the underlying mechanism of RSL3 in PARPi-resistant breast cancer cells, we treated several PARPi-resistant breast cancer cells with varying doses of RSL3. The regulatory proteins of STAT3 were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Immunoprecipitation and ubiquitination assay were performed to identify the STAT3 ubiquitination levels. Results: Recently, we identified that RSL3, a ferroptosis activator, exhibits potent antitumor activity against PARPi-resistant breast cancer. Yet, its underlying mechanism remains unclear. Here, we demonstrate that RSL3 directly targets STAT3 and promotes its degradation via the ubiquitination pathway, leading to increased LC3-II levels and decreased p62 expression. These changes ultimately enhance autophagy, which at least partially contributes to elevated apoptosis. Rescue experiments confirmed that STAT3 overexpression reverses RSL3-induced autophagy and apoptosis. Conclusions: Our findings highlight RSL3 as a promising therapeutic agent and STAT3 as a potential target for treating PARPi-resistant breast cancer. Full article

Background: Sentinel lymph node biopsy (SLNB) is the standard axillary staging procedure in clinically node-negative breast cancer but remains invasive, non-therapeutic and increasingly questioned in contemporary de-escalation algorithms. After neoadjuvant chemotherapy (NACT), however, the safety of omitting SLNB solely on the basis of a negative axillary ultrasound (AUS) is uncertain, particularly across molecular subtypes with heterogeneous chemosensitivity. This study evaluated the diagnostic performance of preoperative AUS after NACT and explored clinicopathological and biological factors associated with SLNB positivity in ultrasound-negative axillae. Methods: In this single-centre retrospective cohort, 135 women with invasive breast cancer who received NACT followed by surgery (2022–2024) were analysed. To avoid spectrum bias, 77 patients with clipped, cytologically or histologically proven node-positive disease at baseline were excluded from the main analysis. All patients underwent preoperative AUS and definitive axillary staging. Ninety-six women with ultrasound-negative axillae who proceeded to SLNB constituted the primary study population. Oestrogen receptor (ER), progesterone receptor (PR), HER2, Ki-67 and immunohistochemistry-based molecular subtype were recorded. Receiver operating characteristic (ROC) analysis and uni/multivariable logistic regression were used as exploratory tools to identify factors associated with SLNB positivity. Results: In the overall cohort, AUS sensitivity, specificity, negative predictive value and false-negative rate for axillary metastasis were 47.8%, 90.9%, 62.5% and 52.2%, respectively. Among ultrasound-negative axillae, SLNB was positive in 37.5%. Compared with SLNB-negative patients, those with SLNB metastases more frequently harboured an intratumoural ductal carcinoma in situ (DCIS) component, showed higher ER/PR expression and lower Ki-67, and were predominantly luminal A or luminal B/HER2−, whereas AUS performance appeared more favourable in HER2-enriched and triple-negative tumours. ROC-derived cut-offs for ER (82.5%), PR (25.0%) and Ki-67 (17.5%) provided only moderate discrimination (area under the curve 0.68–0.70). In multivariable analysis, absence of a DCIS component and low PR expression were independently associated with reduced odds of SLNB positivity, suggesting that DCIS and high PR may act as indicators of residual nodal risk in ultrasound-negative axillae. All estimates are limited by sample size and wide confidence intervals and should be interpreted as hypothesis-generating. Conclusions: Preoperative AUS alone cannot reliably exclude sentinel lymph node metastasis after NACT, particularly in luminal A and luminal B/HER2− tumours with strong hormone receptor expression and a low proliferative index. Until prospective, biology-stratified trials confirm the safety of omission, SLNB should not be withheld solely on the basis of a negative AUS in these subtypes. Axillary management after NACT should systematically integrate both imaging findings and tumour biology when considering further de-escalation of surgery. Full article

Background: Early breast cancer outcomes have improved substantially, yet surgery may carry physical and psychosocial costs. Cryotherapy has gained attention as a minimally invasive alternative to surgery for select patients with breast cancer: particularly, those with small, unifocal, hormone receptor-positive tumors. Given rapidly expanding but heterogeneous reports, this state-of-the-art review therefore aims to synthesize information on how breast cryotherapy is performed, for whom it is most suitable, what outcomes to expect, and where evidence is still immature. Methods: We queried MEDLINE (via PubMed), Embase (via Ovid), and the Cochrane Library up to January 2025, using terms related to “breast neoplasms,” “cryotherapy,” and “cryoablation.” Eligible studies included clinical trials, cohort studies, and case series reporting outcomes of cryotherapy in breast cancer. Data were extracted on patient characteristics, procedural parameters, recurrence, survival, and complications. The risk of bias was assessed using the MINORS tool, and certainty of evidence was appraised with the GRADE framework. Results: A total of thirty one studies (comprising 1357 patients) formed the evidence corpus summarized here. Most involved early-stage, hormone receptor-positive breast cancers ≤ 2 cm treated with percutaneous cryoablation. Local recurrence, defined as any ipsilateral breast tumor recurrence confirmed radiologically or histologically, ranged from 0 to 68.8%, with smaller, unifocal tumors achieving the best control. Overall survival exceeded 80% in early-stage disease, while complications were generally minor, including bruising, hematoma, and skin erythema. Patient satisfaction was high, with favorable cosmetic outcomes reported in limited studies. However, the follow-up duration ranged from 1 month to 10 years (with nearly half < 1 year), and protocols varied substantially across studies. In summary, breast cryotherapy appears safe and can achieve encouraging local control and cosmetic results in carefully selected early-stage cases. Its role in aggressive subtypes, larger or multifocal disease, and as part of multimodal regimens requires further study. Conclusions: Standardized protocols, imaging/reporting conventions, and longer follow-up with patient-reported outcomes are needed to advance the field and further define where cryotherapy can appropriately de-escalate surgery. Full article