Search Results (615)

Background/Objectives: Breast cancer affects working-age women not only through treatment and survival but also through health-related quality of life (HRQoL), work capacity and informal caregiving needs. Evidence from Central and Eastern Europe remains limited. This study estimated the indirect societal burden of breast cancer among working-age women in Croatia and reported economic indirect costs separately from monetised HRQoL/welfare loss. Methods: A multicentre cross-sectional study conducted in 2024 included women aged 18–65 years receiving outpatient oncology care at two tertiary centres in Croatia. HRQoL was assessed with the EuroQol five-dimension five-level instrument (EQ-5D-5L) and compared with Croatian general-population norms. Utility decrements were annualised and monetised using a national willingness-to-pay threshold of €17,000 per quality-adjusted life year (QALY). Work productivity impairment was measured using the Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire and valued, together with informal care, using the human-capital approach. Deterministic sensitivity analyses and approximate 95% confidence intervals were used to show how the estimates changed under key assumptions. Results: A total of 271 women participated (mean age 51.3 years among age-eligible records). Mean EQ-5D-5L utility was 0.76 versus 0.91 in the general population, corresponding to an annual QALY loss of 0.15 and a monetised HRQoL/welfare loss of €2550 per patient-year (95% CI €2083–€3017). Among employed participants, mean overall work productivity loss was 43.9% (842.9 h/year), equivalent to €7333 annually (95% CI €6311–€8355). Informal caregiving was reported by 54.7% of participants, with mean annual costs of €1566 (95% CI €1269–€1863). Economic indirect costs were €8899 per patient-year (95% CI €7835–€9963). In an extended welfare-inclusive scenario, the estimated burden was €11,449 per patient-year (95% CI €10,287–€12,611), corresponding to an illustrative national estimate of €86 million (95% CI €77–€95 million; 0.11% of gross domestic product). Conclusions: Breast cancer in working-age women imposes a substantial societal burden in Croatia, driven by reduced HRQoL, productivity losses and informal caregiving needs. These findings support taking societal burden into account in public health planning, survivorship care and health policy decision-making. Full article

Background/Objectives: Breast cancer is the most prevalent malignancy among women worldwide and remains a major cause of morbidity and mortality. Conventional treatments, while effective, often produce physical and psychological adverse effects that impair quality of life. Complementary therapies (CTs) have gained prominence as supportive strategies to mitigate these effects. This systematic review aimed to evaluate the potential benefits of CTs in women with breast cancer undergoing or having completed chemotherapy and radiotherapy. Methods: Following PRISMA 2020 guidelines and Cochrane standards, a systematic search was conducted in PubMed, CINAHL, Web of Science, and Scopus for studies published up to March 2026. Randomized controlled trials assessing CTs in breast cancer patients were included. Methodological quality was appraised using the PEDro scale, and risk of bias was evaluated using the Cochrane RoB 2 tool. Results: Thirty-two RCTs met the inclusion criteria. The interventions included acupuncture and related techniques, mindfulness-based therapies, massage, dance–movement therapy, music therapy, slow breathing, prayer, and natural products. Overall, CTs produced improvements in pain, fatigue, anxiety, depression, sleep quality, and social well-being, though the effects were sometimes therapy-specific and varied. Conclusions: Complementary therapies represent non-pharmacological strategies that may offer potential benefits across physical, emotional, and social outcomes in women with breast cancer. However, mixed results in certain therapies indicate that conclusions must be drawn cautiously. Future research should pursue methodological consistency and longer follow-ups. Full article

Breast cancer remains the most frequently diagnosed malignancy among women worldwide, while metabolic dysfunction-associated steatotic liver disease (MASLD) represents the leading cause of chronic liver disease, reflecting a global burden of metabolic dysfunction. Increasing evidence suggests that MASLD is associated with breast cancer development and progression; however, whether this relationship reflects an independent effect of hepatic metabolic dysfunction or the broader metabolic environment remains uncertain. This review synthesizes current epidemiological, clinical, and mechanistic data linking hepatic metabolic dysfunction to breast carcinogenesis. Population-based studies consistently demonstrate an association between hepatic steatosis and increased breast cancer incidence, particularly in postmenopausal and metabolically vulnerable populations, as well as poorer oncological outcomes. Mechanistically, MASLD promotes a systemic pro-tumorigenic environment through interconnected pathways, including insulin resistance, hormonal dysregulation with increased estrogen bioavailability, chronic inflammation, oxidative stress, lipid metabolic reprogramming, and gut–liver axis disruption. Hepatokines, particularly fibroblast growth factor 21 (FGF21), emerge as key mediators of tumor progression and potential biomarkers of metabolic vulnerability, while Fetuin-A and angiopoietin-like protein 8 (ANGPTL8) further support the liver’s endocrine role in oncogenic signaling. Preclinical evidence highlights fatty acid oxidation as a metabolic dependency in aggressive breast cancer subtypes, suggesting novel therapeutic targets. Despite consistent associations, causality remains unproven. Future prospective studies are needed to determine whether targeting metabolic dysfunction can improve breast cancer prevention and outcomes. Full article

Background/Objectives: Formalin-fixed paraffin-embedded tissue is widely used in pathology and molecular diagnostics, yet its variable quality can critically influence the accuracy of sequencing-based analyses. This study investigated pre-analytical and analytical factors that can affect exome sequencing performance in a Brazilian multicenter cohort of patients with breast cancer and prostate adenocarcinoma. Methods: Tumor samples were reviewed for diagnostic confirmation, and those with a minimum cellularity of 20% underwent DNA extraction, fluorometric quantification, fragmentation analysis, and exome sequencing. Pre-analytical parameters, including tumor content, DNA yield, and fragmentation profile, were recorded and correlated with sequencing results. Results: Only 36.7% of all analyzed samples (163/444) generated valid whole-exome sequencing data, corresponding to 55.6% of those that proceeded to sequencing (163/293). Although 94.5% of specimens met the minimum ≥20% cellularity threshold and 66.0% advanced to sequencing, a substantial proportion failed to yield usable exome data. Successful sequencing was associated with shorter storage durations (p < 0.001) and superior analytical parameters (higher autosomal coverage, longer read lengths, lower duplication rates, and higher target coverage at ≥500× and ≥100×; p < 0.001). Detailed fixation-related variables (e.g., formalin type, fixation time, ischemia time) were not consistently available across centers, representing a major limitation for causal interpretation of pre-analytical effects. Conclusions: Our study identified a high failure rate in sequencing archival tissue, highlighting the need to prioritize more recently collected specimens and refine standardized sample handling protocols to maintain DNA integrity. These improvements are essential for optimizing sequencing workflow performance and feasibility in real-world settings. Full article

Background/Objectives: Breast cancer (BC) is a highly prevalent neoplasm worldwide. Despite the wide range of therapeutic options currently available, it remains the leading cause of cancer-related mortality among women. Capecitabine, a prodrug of 5-fluorouracil (5-FU), is widely used in the treatment of advanced BC. However, despite its efficacy, capecitabine exhibits considerable interindividual variability in therapeutic response. This study aimed to evaluate the effect of single-nucleotide polymorphisms (SNPs) in genes involved in capecitabine bioactivation on progression-free survival (PFS) in patients with BC. Methods: An ambispective cohort study was conducted. Four relevant SNPs in the CES1, CDA, and TYMP genes were analyzed in 85 Caucasian patients with BC using real-time polymerase chain reaction (PCR) with TaqMan^® probes. Results: A significant association was observed between shorter PFS and the GA genotype of the CES1 rs71647871 SNP (p = 0.010; HR = 7.46; 95% CI = 1.24–122.52), as well as with the TT genotype of the CDA rs602950 SNP (p = 0.009; HR = 3.50; 95% CI = 1.36–9.03). Conclusions: These findings suggest that CES1 rs71647871 and CDA rs602950 may serve as predictive biomarkers of capecitabine effectiveness in patients with BC. Further studies involving larger cohorts are needed to validate these findings and generate additional evidence to support their potential implementation in clinical practice. Full article

Background: The sensitivity of mammography screening is compromised in women with dense breast tissue. Supplemental ultrasound (S-US) can enhance cancer detection, but evidence regarding its feasibility, harms, and benefits within Western population-based screening programs remains limited. Methods: This pragmatic, prospective controlled trial was integrated into the German national mammography screening program across 16 sites. Breast density was assessed using automated AI software. Women with “critically dense” breasts (top 15–20%) were offered handheld supplemental S-US in addition to mammography (MXUS). The control group (MX-only) comprised women with comparable densities who did not receive S-US. Primary outcomes included cancer detection rate (CDR), recall rate, biopsy rate, and short-term follow-up recommendations. Results: From May 2020 to March 2024, 25,341 women underwent MXUS, while 38,529 received MX-only. The CDR was significantly higher in the MXUS group, at 10.7 per 1000 (95% CI: 9.4–12.0) compared to 7.2 per 1000 (95% CI: 6.4–8.1) in the MX-only group, yielding an incremental CDR of 3.5 per 1000 (95% CI: 1.9–5.0). However, MXUS led to higher rates of recall (6.6% vs. 5.4%), biopsies (3.2% vs. 1.5%), and short-term follow-up recommendations (0.9% vs. 0.5%). Conclusions: Implementing quality-assured S-US for women with critically dense breasts substantially increases the detection of invasive cancers, but also raises false positives. While these results support density-adapted screening, the high resource intensity suggests that future strategies should optimize risk stratification to target S-US more selectively. Long-term data are required to confirm clinical benefits. Full article

Breast cancer represents a major public health problem worldwide. Despite radical surgery for localized disease, a substantial proportion of patients experience disease recurrence. The aim of this study was to evaluate the expression of the mammaglobin and CK19 genes in sentinel lymph node biopsies from patients with early breast cancer. This descriptive study included 301 sentinel lymph node biopsies from patients with stage I–II breast cancer treated at the San Carlos Clinical Hospital in Madrid, Spain. Metastases were identified using conventional histopathology (H&E), immunohistochemistry (IHC), and molecular detection of mammaglobin and CK19 using PCR-based methods. Associations between variables were assessed using Fisher’s exact test with a 95% confidence level. Statistical analyses were performed using STATA 12.0. The predictive value for metastatic involvement was 12.29% for CK19 and 16.61% for mammaglobin, increasing to 19.27% when conventional staining was combined with immunohistochemistry. The overall sensitivity was 68.9%, and the specificity was 93.42%. Mammaglobin showed slightly better diagnostic performance than CK19, and the combined molecular detection of both genes improved diagnostic accuracy when compared with individual markers. Intraoperative molecular evaluation of sentinel lymph nodes using mammaglobin and CK19 is comparable to conventional histopathological assessment combined with immunohistochemistry. The combined RT-PCR detection of both genes improves diagnostic performance and represents a clinically useful complementary tool for the detection of metastatic involvement in early breast cancer. Full article

TRAF3 (TNF Receptor Associated Factor 3) is a regulator of NF-κB signaling, acting mainly as an inhibitor of the alternative NF-κB pathway. While TRAF3 has a well-established role in immune function, mainly via B- and T-lymphocyte regulation, its roles in cancer remain unclear. Breast cancer is the most common malignancy in women and a neoplasm displaying high levels of intratumoral heterogeneity. Identifying and understanding key molecules at the interface of breast cancer cells and the immune system is crucial for advancing therapeutic strategies for breast cancer patients. Here, by employing publicly available breast cancer datasets, breast cancer cell lines stably expressing TRAF3, mass spectrometry analysis in combination with functional assays, co-culture systems, and signal pathway characterization, we sought to assess the specific role of TRAF3 in breast cancer cells and how TRAF3-expressing breast cancer cells affect their immune microenvironment. Our results indicate that TRAF3 protein overexpression inhibits colony formation through apoptosis regulation. Proteome analysis for TRAF3 interactors and over-representation analysis identified multiple protein complexes related to cell cycle, apoptosis, and immune responses. Furthermore, TRAF3-expressing breast cancer cells displayed reduced levels of PD-L1 and when co-cultured with PBMCs induced a pro-inflammatory profile with increased CD16-NK cells and higher levels of IFN-γ and TNF-α and lower IL-10 and Tregs in the culture. These findings further expand the role of TRAF3 in breast cancer, not only as a regulator of EMT and survival of cancer cells, but also as a modulator of the tumor-immune microenvironment. Full article

Phyllodes tumours (PTs) of the breast are rare fibroepithelial neoplasms with potentially aggressive behaviour, characterised by rapid growth, a significant risk of local recurrence, and occasional metastatic spread. Optimal management remains controversial, particularly regarding surgical margins, adjuvant radiotherapy, and the relevance of molecular markers in predicting tumour behaviour. A PRISMA 2020-guided qualitative systematic review was conducted of studies published between January 2000 and December 2024 in PubMed/MEDLINE, Scopus, and Web of Science. Eligible studies included malignant PTs of the breast and addressed at least one of the following domains: molecular pathology, surgical margins and local recurrence, adjuvant radiotherapy, or predictors of recurrence and metastasis. A clinical case of malignant PT treated at our institution is presented as an illustrative study. Thirty-four studies met the inclusion criteria. Evidence suggests that margin status, stromal proliferative activity, and selected molecular markers influence recurrence risk. Several retrospective studies suggest that adjuvant radiotherapy may improve local control in selected high-risk malignant PTs, although the evidence remains heterogeneous, retrospective, and potentially affected by treatment-selection bias, and no consistent survival benefit has been demonstrated. Molecular alterations, including MED12 mutations, TERT promoter mutations, TP53 alterations, and increased Ki-67 expression, have been associated with tumour progression and aggressive behaviour. A 44-year-old woman presented with a 2.4 cm left breast mass on radiological examination. Lumpectomy revealed a malignant PT with stromal hypercellularity, nuclear atypia, and a mitotic index of 20/10 HPF with close margins. Immunohistochemistry showed positivity for CD99, Bcl-2, and CD34 with a Ki-67 proliferation index of 20%. The patient underwent wide local re-excision followed by adjuvant radiotherapy (60 Gy), and at 24-month follow-up, the patient remained disease-free. Evidence synthesis highlights the importance of complete surgical excision, multidisciplinary management, and consideration of adjuvant radiotherapy in selected malignant PTs. Emerging molecular profiling may contribute to improved biological understanding and future risk stratification of malignant PTs, although its routine clinical utility remains to be validated in prospective studies. Full article

Background/Objectives: Early identification of breast cancer patients who are likely or unlikely to benefit from neoadjuvant chemotherapy (NAC) remains clinically important because ineffective treatment may delay definitive surgery and expose patients to unnecessary toxicity. Quantitative ultrasound (QUS) radiomics offers a contrast-free and repeatable method for extracting tissue-sensitive imaging biomarkers from raw ultrasound data. This study aimed to evaluate whether baseline QUS radiomic features and early treatment-induced changes could predict a pathologic response to NAC in a real-world single-center cohort. Methods: We designed a prospective observational study including 96 consecutive women with biopsy-proven stage II–III breast cancer treated with NAC at Victor Babes University of Medicine and Pharmacy Timisoara. All patients underwent standardized QUS examinations before treatment and again at week 2. The response was defined pathologically at surgery as residual cancer burden class 0/I versus II/III. Clinical, histopathologic, and QUS variables were compared between responders and non-responders. Group comparisons used Student’s t test, Mann–Whitney U test, chi-square testing, and Fisher’s exact test where appropriate. Multivariable logistic regression was used to identify independent predictors of response. Model discrimination was summarized using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: Forty-three patients (44.8%) were classified as responders and 53 (55.2%) as non-responders. Responders had higher baseline Ki-67 values (47.8 ± 13.1% vs. 41.9 ± 13.0%, p = 0.033), lower baseline homogeneity (0.3 ± 0.1 vs. 0.4 ± 0.1, p = 0.010), and higher peritumoral heterogeneity (0.9 ± 0.1 vs. 0.8 ± 0.2, p = 0.027). At week 2, responders showed larger increases in mid-band fit (3.0 ± 0.8 vs. 1.2 ± 0.8 dB, p < 0.001), greater entropy change (0.7 ± 0.2 vs. 0.2 ± 0.2, p < 0.001), more pronounced spectral intercept reduction (−3.5 ± 1.4 vs. −1.2 ± 1.3, p < 0.001), and greater tumor shrinkage (−24.3 ± 7.0% vs. −11.1 ± 5.7%, p < 0.001). In multivariable analysis, Δ MBF and Δ entropy remained independent predictors of pathologic response. The combined clinical-plus-QUS model achieved an AUC of 0.89. Conclusions: Baseline microstructural heterogeneity and very early QUS-derived treatment changes were strongly associated with the pathologic response to NAC. These findings support the potential role of QUS radiomics as a low-cost, repeatable early-response biomarker in breast cancer. Full article

Background: Fibroblast growth factor 21 (FGF21) is a peptide hormone that is synthesized by several organs and regulates energy homeostasis, including reducing fat mass and lowering hyperglycemia, insulin resistance and dyslipidemia. It also increased metabolic syndrome (MS) and cardiovascular risk in breast cancer (BC) survivors treated with aromatase inhibitors (AIs) aimed at reducing cancer recurrence. We evaluated whether blood FGF21 concentration is associated with MS and its five criteria in postmenopausal women treated with AIs, and whether this persists after multimodal interventions that reduce MS. Methods: A quasi-experimental longitudinal study in 31 postmenopausal women with localized BC on Ais, assessed via a 12-week multimodal program. Their MS was evaluated per the NCEP-ATP III guidelines (waist circumference, blood pressure, fasting glucose, triglycerides, HDL-cholesterol). Plasma FGF21 was measured pre/post-intervention via fasting blood samples, centrifugation, and ELISA assay. Results: Pre-intervention FGF21 median: 377.62 pg/mL (38.40–1616.42). Plasma FGF21 concentrations positively correlated with MS criteria number pre- and post-intervention (all p < 0.05). Linear regression confirmed pre-intervention MS criteria (β = 127.262, p = 0.006) and antihypertensive drugs as predictors of post-FGF21 levels. Analysis of individual MS criteria revealed significant associations with blood pressure (p = 0.028 and p = 0.022 for systolic and diastolic pressure, respectively) and fasting glucose changes (p = 0.008). Conclusions: Plasma FGF21 may act as a biomarker for monitoring exercise-based interventions which reduce MSs, particularly hypertension and hyperglycemia, in AI-treated BC survivors. Full article

Background: Radiologic–pathologic discordance remains an important concern owing to the absence of standardized guidelines. This systematic review aimed to summarize the prevalence of discordant benign outcomes, defined as suspicious imaging findings with benign biopsy histology insufficient to explain the imaging abnormality, and to quantify malignancy upgrades subsequent to additional tissue assessment. Methods: This review was conducted in accordance with PRISMA 2020 guidelines and was prospectively registered. Eligible studies reported primary patient-level or aggregated data on radiologic–pathologic correlations post-image-guided breast biopsy and provided extractable data on discordant benign prevalence and/or subsequent malignancy upgrades. Results: Twenty-three studies were included. Lesion-/biopsy-based cohorts focused on biopsied abnormalities for analysis. Twelve studies directly estimated discordant-benign prevalence, whereas 11 studies did not, as study designs were discrepant-only, lesion-defined, or excision-restricted. Unselected cohorts with a cohort-wide correlation reported 1.2–5.3% discordant benign prevalence for all biopsies. When restricted to excised lesions, the discordant benign ascertainment rate was 7.4%, representing an excision-ascertained subset rather than the cohort-wide prevalence. Using benign-biopsy denominators, the discordance rate was 1.5–19.2%. Malignancy upgrades among discordant benign lesions ranged from 0 to 100% in selected subsets; however, several clinically relevant cohorts reported representative rates of approximately 20–40%, with some high-risk cohorts exceeding 50%. Conclusions: Discordant benign biopsy results are rare in unselected biopsy populations but carry a clinically meaningful upgrade risk, which warrants structured radiologic–pathologic correlation and prompt diagnostic resolution through repeat sampling or excision. Improvements in comparability and management algorithms require standardized definitions, uniform denominators aligned with all biopsied lesions, and prospective multicenter designs. Full article

Background: Germline CDKN2A variants are associated with Familial Atypical Mole-Malignant Melanoma (FAMMM) syndrome. This syndrome involves an increased risk of melanoma, pancreatic cancer, and, in specific populations, duodenal cancer, breast cancer, and astrocytoma. The CDKN2A (c.146T>C) variant has been found in hereditary cancer patients within the Mexican population. Furthermore, the phenotype linked to this variant in Mexico differs from that observed in other groups. This study aims to evaluate the founder effect of the CDKN2A (c.146T>C) variant through epidemiological analysis and to describe the phenotype within our population. Patients and Methods: We examined 72 Mexican patients (14 probands from distinct families, 48 relatives, and 10 nonrelated probands) carrying the CDKN2A (c.146T>C) form three hereditary cancer centers between September 2023 and September 2025. Results: Of the 72 individuals analyzed, 52 (72.22%) tested positive. A cancer diagnosis was established in 27 (37.50%) of the individuals analyzed. Breast cancer was the most common neoplasia, accounting for 19 cases (70.37%), followed by melanoma with 4 cases (14.81%) and ovarian cancer with 2 cases (7.40%). Three patients (11.11%) had two distinct primary neoplasms. Conclusions: Based on our findings and the fact that this variant has been reported nearly exclusively in the Mexican population, we conclude that it has a founder effect in this population. Additionally, the phenotype associated with this variant can vary among populations, with breast cancer being the most common carcinoma rather than melanoma among Mexican carriers, highlighting the importance of updating screening guidelines. Full article

Introduction: Breast cancer-related lymphedema (BCRL) affects quality of life (QoL) and increases healthcare costs. Resistance training (RT) is proposed as a preventive strategy, although its safety and effectiveness remain uncertain. Objective: To evaluate the effectiveness and safety of RT in preventing BCRL in women at risk. Methods: MEDLINE, Embase, CENTRAL, PEDro, and LILACS databases were searched from their inception to January 2025, along with the gray literature, trial registries, and preprints. Risk of bias was assessed using RoB 2, and certainty of the evidence (CoE) was assessed using GRADE. Primary outcomes were the occurrence of lymphedema and overall QoL; secondary outcomes included pain, upper limb function, range of motion (ROM), grip strength, and adverse events. Results: Eight RCTs (n = 1131) were included. The effects of RT on lymphedema and arm volume are very uncertain (very low CoE). For QoL, pain, ROM, and grip strength, the findings were inconsistent and uncertain (low to very low CoE). Adverse events were mild and transient, with no serious complications. Conclusion: RT is probably safe in women at risk of developing BCRL. Its preventive effectiveness is highly uncertain. Well-designed RCTs with standardized diagnostic criteria, patient-centered outcomes, and long-term follow-up are needed to establish their role in BCRL prevention with greater certainty. Ethics and dissemination: This study did not require ethical approval. The results will be disseminated through publications in peer-reviewed journals and academic presentations. Registration: PROSPERO (CRD42023455720). Full article

Background: Oncoplastic breast surgery aims to combine oncologic safety with optimal cosmetic outcomes. However, many established techniques require visible anterior breast incisions or substantial tissue rearrangement, which may compromise cosmetic results in selected patients. Posterior access to the breast through the retromammary space may allow tumor excision while preserving the anterior breast envelope. Methods: We report an early clinical experience with Posterior Approach Partial Mastectomy (MAPP), a breast-conserving technique that accesses the lesion through a concealed inframammary or lateral breast crease incision. This single-center retrospective case series included consecutive patients undergoing excision using this approach. Patient selection, surgical technique, and early outcomes—including margin status, complications, and need for re-excision—were evaluated. Results: Eight patients underwent breast-conserving excision using the MAPP technique. Six patients had malignant lesions (invasive ductal carcinoma with or without ductal carcinoma in situ or pure DCIS), while two benign lesions were included for technical completeness. Tumor size ranged from 9 to 78 mm. All malignant cases achieved negative surgical margins (R0), and no patient required re-excision. Posterior access was successfully achieved in all cases using concealed inframammary or lateral crease incisions. One patient experienced minor wound discharge that resolved with conservative management, and no major postoperative complications were observed. Follow-up ranged from 2 to 12 months. Conclusions: Posterior Approach Partial Mastectomy appears to be a feasible oncoplastic approach with encouraging early oncologic outcomes in carefully selected patients undergoing breast-conserving surgery. By preserving the anterior skin envelope and concealing the surgical incision, this technique may offer cosmetic advantages while maintaining oncologic adequacy. Larger studies with longer follow-up are needed to further define its role in oncoplastic breast surgery. Full article