Search Results (990)

Background: Abemaciclib (ABM) in combination with tamoxifen (TAM) is an extremely significant treatment regimen for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. It is approved for patients to reduce the risk of cancer recurrence. A bioanalytical method for the simultaneous determination of this new anti-breast cancer combination and its pharmacokinetic application has not yet been reported. Methods: An ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method was developed for quantifying ABM, TAM, and its metabolites, including abemaciclib active metabolites M2, M18, and M20 and tamoxifen active metabolite N-desmethyl tamoxifen (NDTAM), in rat plasma using econazole as the internal standard (IS). Chromatographic separation was achieved on a Kinetex C18 column (100 × 2.1 mm ID, 2.6 µm) using gradient elution with 5 mM ammonium formate in water (eluent A) and 5 mM ammonium formate in water/methanol (1:9, v/v, eluent B) at a flow rate of 0.4 mL/min. Detection was performed on a TSQ Fortis Plus mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization. Results: The developed method was validated according to the guidance of the FDA. Linearity in rat plasma (ng/mL) was achieved from 1 to 1000 for ABM, TAM, and M20; 3 to 1000 for M2; 5 to 500 for M18; and 1 to 500 for NDTAM; with correlation coefficients ranging from 0.9991 to 0.9931 for all analytes using a weighting factor of 1/X². The lower limit of detection (LLOD) ranged between 0.3 and 1.5 ng/mL for all drugs. The accuracy ranged from 96 to 108% and the precision was less than 7.6% RSD for all analytes. For the first time, the newly developed approach was effectively used in a pharmacokinetic study on the simultaneous oral administration of ABM and TAM in rats that received 30.0 mg/kg of ABM and 8.0 mg/kg of TAM. Conclusions: To the best of our knowledge, this is the first reported UPLC–MS/MS method for the assay of ABM, TAM, and its active metabolites in plasma. This method offers a bioanalytical tool for assessing the pharmacokinetics of ABM and TAM. Therefore, this study makes a definite significant contribution to the field of bioanalytical research. Further validation in human plasma is required for future clinical or therapeutic drug monitoring applications, as the approach was developed in an animal model. Full article

Introduction: Breast cancer is one of the major killers among malignant conditions worldwide, affecting one out of 10 women in industrialized countries and being the leading cause of cancer-related morbidity and mortality in women. The relationships between risk factors and breast cancer development are not exactly known. The selection of the UBC9 gene and its c.73G>A polymorphism (rs11553473) in breast cancer studies is justified by the gene’s critical role in sumoylation, its impact on DNA repair, and its association with aggressive tumor characteristics. UBC9 (SUMO-conjugating enzyme) is frequently overexpressed in breast cancer, often 5–8-fold higher than in normal tissues, where it promotes tumor proliferation, invasion, and metastasis, often in a sumoylation-independent manner. Aim: In the present work, the association of polymorphism in the UBC9 genes c.73G>A with breast cancer risk was investigated. Materials and Methods: In the reported study, paraffin-embedded tumor tissue was collected from women with lymph node-negative (n = 59) and lymph node-positive (n = 41) ductal breast carcinoma. Samples from age-matched, cancer-free women (n = 100) served as controls. The genotypes of the UBC9 c.73G>A polymorphism were determined by ASO-PCR methods. Results: In the present work, a significant positive association between the UBC9 c.73G>A G/A genotype and breast cancer is demonstrated. The variant A allele of UBC9 increased breast cancer risk. Some correlation was observed between the genotypes of UBC9 polymorphism and breast cancer invasiveness. A statistically significant increase was observed regarding G/A heterozygote frequency in stage II patients, according to Bloom–Richardson classification. There were no significant differences in genotype distribution among subgroups defined by TNM stage, histological grade, hormone receptor status, or HER-2 expression. Conclusions: In conclusion, the reported study indicates that the polymorphisms of the UBC9 gene may be positively associated with the incidence of breast cancer. However, further research is needed on larger study populations. Full article

Background/Objectives: The prognostic significance of the uric acid-to-albumin ratio (UAR) in patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has not been adequately investigated. This study aimed to investigate the association between baseline UAR and survival outcomes in this patient population. Methods: This retrospective study included HR-positive/HER2-negative metastatic breast cancer patients treated with ribociclib or palbociclib at Necmettin Erbakan University between May 2020 and April 2025. UAR was calculated by dividing the serum uric acid level (mg/dL) by the serum albumin level (g/dL). Based on receiver operating characteristic (ROC) analysis, the optimal cut-off value for UAR was identified as 1.0 (AUC = 0.67; sensitivity 68%; specificity 58%). Patients were subsequently classified into two groups as UAR < 1 and UAR ≥ 1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared with the log-rank test. Independent prognostic factors were evaluated using Cox regression analyses. Results: A total of 118 eligible patients were included in the analysis, including 34 (28.8%) in the UAR < 1 group and 84 (71.2%) in the UAR ≥ 1 group. The proportion of postmenopausal patients was significantly higher in the UAR ≥ 1 group (p = 0.01). Kaplan–Meier analysis showed that median PFS was not reached in the UAR < 1 group, whereas it was 33.05 months in the UAR ≥ 1 group (log-rank p = 0.06). Median OS was not reached in the UAR < 1 group and was 50.7 months in the UAR ≥ 1 group (p = 0.017). Multivariate Cox regression analysis demonstrated that UAR < 1 was associated with improved PFS (HR = 0.65; 95% CI: 0.34–0.89; p = 0.04). Postmenopausal status emerged as an independent adverse prognostic factor for PFS (HR = 1.92; 95% CI: 1.10–4.05; p = 0.04). In addition, UAR < 1 was associated with a reduced risk of mortality in the OS analysis (HR = 0.61; 95% CI: 0.26–0.87; p = 0.01). Conclusions: Lower baseline UAR was associated with more favorable survival outcomes in HR-positive/HER2-negative metastatic breast cancer patients treated with CDK4/6 inhibitors. As an inexpensive and easily accessible biomarker derived from routine laboratory parameters, UAR may provide additional prognostic information for clinical risk stratification. Full article

Background/Objectives: Capivasertib is a selective pan-AKT inhibitor recently approved in combination with fulvestrant for the treatment of hormone receptor-positive (HR+)/HER2- breast cancer with alterations in the PI3K/AKT pathway. The PI3K/AKT/mTOR signaling cascade represents a critical indication of endocrine resistance and tumor progression in this subtype of breast cancer. The present review summarizes current clinical data regarding the efficacy of capivasertib, either as monotherapy or in combination with other therapeutic agents and discusses emerging biomarkers and mechanisms of resistance. Methods: A literature search of the PubMed database was conducted to identify clinical trials evaluating capivasertib in breast cancer. Studies on capivasertib as monotherapy or in combination with fulvestrant, paclitaxel, or olaparib were included. Results: Findings from phase I–III clinical trials indicate that capivasertib in combination with fulvestrant significantly prolongs progression-free survival in patients with HR+/HER2- advanced breast cancer, particularly in tumors containing PIK3CA, AKT1, or PTEN alterations. Drug combination approaches with paclitaxel or olaparib have demonstrated additive or synergistic effects in triple-negative and DNA repair-deficient contexts, respectively. Monotherapy studies confirm effective pathway inhibition with modest clinical benefit, primarily in AKT1-mutant tumors. Translational analyses suggest that persistent mTORC1-mediated protein synthesis and compensatory signaling activation contribute to acquired resistance. Conclusions: Capivasertib constitutes a clinically validated therapeutic approach for the inhibition of AKT signaling in breast cancer. Its efficacy is most evident when combined with endocrine therapy; however, optimization of patient selection and rational combination strategies remains necessary to overcome resistance associated with mTORC1 activation and signaling redundancy. Full article

Introduction: In the treatment of hormone receptor-positive (HR+), HER2-negative (HER2−) metastatic breast cancer (MBC), the current guidelines recommend endocrine therapy combined with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors as the preferred first-line treatment to preserve quality of life. Ribociclib is a CDK4/6 inhibitor that has been used in combination with aromatase inhibitors or fulvestrant in patients with HR+, HER2− metastatic breast cancer. Various adverse drug reactions associated with ribociclib have been reported, including cutaneous reactions, hepatotoxicity, and hematologic toxicity. In this study, we aimed to evaluate the clinical manifestations and risk factors of dermatologic toxicities in patients with metastatic breast cancer treated with ribociclib. Methods: This retrospective study included patients with metastatic/recurrent breast cancer who were prescribed ribociclib from April 2021 to December 2024 at a single institution. We retrospectively reviewed the medical records of these patients to identify the frequency of cutaneous adverse events, the time of onset, and the clinical characteristics of skin reactions. Logistic regression analysis was performed on several clinical factors, including body surface area (BSA) and concomitant medications, to identify risk factors associated with the occurrence of cutaneous adverse events. Results: A total of 110 patients with MBC were enrolled during the study period. The median age was 53 years (range, 28–82); all 110 patients (100.0%) were female; the median BSA was 1.56 m² (range, 1.29–2.07); and 32 patients (29.1%) were premenopausal. Ribociclib plus letrozole was administered in 48 patients (43.6%) and ribociclib plus fulvestrant in 29 patients (26.4%). An additional 33 patients (30.0%) received ribociclib plus letrozole with a gonadotropin-releasing hormone (GnRH) agonist. Cutaneous adverse events occurred in 29 patients (26.4%), and the median time to onset was 84 days (range, 3–498). The cutaneous adverse event patterns included pruritus, erythematous macular rash, eczematous rash/contact dermatitis, vitiligo, urticarial reactions, polymorphous light eruption, toxic epidermal necrolysis (TEN), and desquamation. Grade 1 or 2 cutaneous adverse events occurred in 93.1% of patients; Grade 3 toxicity occurred in one patient; and Grade 4 toxicity, namely toxic epidermal necrolysis (TEN), was reported in one patient. Dose reduction was required in three patients (10.3%), and permanent discontinuation of ribociclib occurred in one patient. Clinical improvement was achieved in the majority of patients (86.2%) with cutaneous adverse events following supportive care. Logistic regression analysis revealed that age, Eastern Cooperative Oncology Group (ECOG) performance status, body surface area (BSA), treatment regimen, and use of cholesterol-lowering medications were not independently associated with the development of cutaneous adverse events. Conclusion: CDK4/6 inhibitors represent one of the most important treatment options for HR+/HER2− metastatic breast cancer. Regardless of their clinical efficacy, cutaneous adverse events remain a common source of patient discomfort. Therefore, careful clinical attention and appropriate supportive care are essential to improve patients' quality of life. Full article

Objective: This study aimed to evaluate the prognostic significance of positron emission tomography/computed tomography (PET/CT)-derived sarcopenia in patients with hormone receptor-positive, HER2-negative metastatic breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Methods: This retrospective single-center study included 77 patients treated between January 2018 and March 2025. Sarcopenia was assessed using skeletal muscle index (SMI) at the L3 level on fluorodeoxyglucose (FDG) PET/CT. Patients were classified as sarcopenic or non-sarcopenic. Clinical, nutritional parameters including body mass index (BMI) and prognostic nutritional index (PNI), and inflammatory parameters including pan-immune inflammation value (PIV) were analyzed. The primary endpoint was progression-free survival (PFS). Results: Sarcopenia was present in 35.1% of patients. After a median follow-up of 38 months, sarcopenic patients had significantly shorter PFS compared with non-sarcopenic patients (18 vs. 38 months; HR: 2.37, 95% CI 1.12–4.99, p = 0.02, multivariable analysis). In multivariable analysis, sarcopenia, recurrent disease, brain metastasis, and liver metastasis were independent predictors of PFS. No significant association was observed between sarcopenia and overall survival. BMI, PNI, and PIV were not associated with survival outcomes. Toxicity profiles were comparable between groups. Conclusions: PET/CT-derived sarcopenia may be a prognostic factor for PFS in patients receiving CDK4/6 inhibitors, whereas conventional nutritional and inflammatory markers are not. These findings support the clinical utility of imaging-based body composition assessment. Prospective studies incorporating functional measures of sarcopenia are warranted. Full article

Advances in molecular oncology have reshaped the management of breast cancer through the development of pathway-specific targeted therapies. In particular, inhibition of HER2, CDK4/6, and PI3K signaling has yielded substantial clinical benefits in molecularly defined patient populations. This review provides an integrated analysis of three representative agents—trastuzumab, abemaciclib, and alpelisib—highlighting their distinct mechanisms of action, clinical efficacy, and translational relevance in breast cancer, with contextual insights into gynecologic oncology. Evidence from pivotal clinical trials and emerging translational studies demonstrates that trastuzumab remains a cornerstone of HER2-positive breast cancer treatment, while also showing activity in HER2-amplified gynecologic malignancies. Abemaciclib, a selective CDK4/6 inhibitor, has significantly improved outcomes in hormone receptor–positive breast cancer and is being actively explored in tumors characterized by cell cycle dysregulation, including endometrial and ovarian cancers. Alpelisib, targeting the PI3Kα isoform, provides meaningful benefit in PIK3CA-mutated breast cancer and represents a promising strategy in gynecologic tumors with aberrant PI3K/AKT/mTOR pathway activation. Collectively, these agents exemplify precision oncology approaches that align therapeutic strategies with tumor biology. Their integration into biomarker-driven, multimodal treatment frameworks underscores a paradigm shift toward personalized cancer care across breast and gynecologic malignancies. Particular emphasis is placed on the translation of molecular diagnostics into clinical decision-making, including patient selection, resistance mechanisms, and sequencing strategies within evolving precision oncology frameworks. Ongoing clinical and translational research will be critical to refine combination strategies, overcome resistance mechanisms, and identify predictive biomarkers to further optimize patient outcomes. Full article

Background/Objectives: Cardiovascular disease (CVD), particularly coronary artery disease (CAD), is increasingly linked to microvascular inflammation driven by interactions between immune, vascular, and neuroendocrine systems. Mast cells (MCs), strategically positioned near blood vessels, play pivotal roles in this process through the release of inflammatory and vasoactive mediators, contributing to increased vascular permeability, endothelial dysfunction, and tissue inflammation in conditions including ischemia–reperfusion (I/R) and CVD. This comprehensive review examines the cellular and molecular mechanisms underlying MC-mediated microvascular inflammation, with emphasis on neuroimmune regulation through the heart–brain axis, and evaluates the therapeutic potential of flavonoids. Methods: A review of in vitro, animal, and clinical studies was conducted to assess MC-mediated cardiovascular pathology and the pharmacological effects of natural flavonoids on MC activation and microvascular inflammation. Results: Psychological and physical stress activates hypothalamic corticotropin-releasing hormone (CRH) signaling, directly triggering coronary MC degranulation via CRHR-1 and CRHR-2 receptors, while co-released neuropeptides, including neurotensin and urocortin, amplify this neuroimmune cascade. Traumatic brain injury, autonomic dysregulation, and atrial fibrillation further perpetuate this bidirectional heart–brain axis, linking neurological stress to microvascular injury and adverse cardiac remodeling. An autocrine–paracrine CRH amplification loop sustains chronic coronary microvascular inflammation, contributing to heart failure with preserved ejection fraction (HFpEF) and MC activation disease (MCAD)-related cardiovascular manifestations. Natural flavonoids were found to inhibit MC activation, suppress inflammatory mediator synthesis, and protect microvascular integrity through multiple molecular targets, including calcium signaling, transcription factors, oxidative stress pathways, and CRHR-1-mediated neuroimmune signaling. Conclusions: While challenges remain regarding bioavailability and standardization, multi-compound formulations targeting multiple risk factors hold promise for preventing CVD progression. Future research directions for advancing these natural compounds toward clinical implementation are identified. Full article

Exosomal microRNAs (miRNAs) are key mediators of intercellular communication in the breast cancer tumor microenvironment (TME), facilitating bidirectional signaling between malignant cells and the desmoplastic stroma. This review explores current evidence on their dual roles as drivers of stromal remodeling and as circulating biomarkers of therapeutic resistance across major breast cancer subtypes, including triple-negative breast cancer (TNBC), hormone receptor-positive (ER+/PR+) disease, and HER2-amplified tumors. We outline how miR-9, miR-21, and miR-181 family members promote cancer-associated fibroblast (CAF) activation, increase extracellular matrix (ECM) stiffness, and sustain a reverse Warburg phenotype. We then detail subtype-specific resistance mechanisms: miR-181 family members suppress BCLAF1 to block doxorubicin-induced apoptosis; miR-221/222 downregulates ESR1 and p27Kip1 to confer tamoxifen resistance; miR-155 impairs homologous recombination in TNBC; and miR-1246 sustains PI3K/AKT signaling in HER2-positive disease. We also evaluate circulating exosomal miRNA panels as liquid biopsy tools for predicting chemotherapy response and tracking resistance emergence. Finally, we discuss therapeutic strategies including antagomirs, miRNA replacement therapy and engineered exosome platforms, and address key challenges such as assay standardization and regulatory hurdles, that must be overcome for clinical translation. Full article

Background/Objectives: Genetic testing in Human Epidermal Growth Factor Receptor 2-negative (HER2−) metastatic breast cancer (mBC) is necessary to enable optimal treatment choices including poly(ADP-ribose)polymerase inhibitors (PARPis). The present study evaluated the implementation of genetic testing in a real-world setting to reveal and subsequently allow targeting of potential inadequacies and risk factors for low testing frequency. Methods: We performed a retrospective analysis including HER2− mBC patients treated at a single academic center starting from 10 April 2019 (date of European Medicines Agency (EMA) approval of Olaparib for germline breast cancer gene mutant (gBRCAm) HER2− mBC) to 7 September 2021. The primary objective of the study was to evaluate the rate of HER2− mBC patients that were recommended to undergo genetic testing by the multidisciplinary tumor board (MTB). The secondary objective was to identify factors that were associated with a higher likelihood of having undergone genetic testing. Results: In total, 47.6% (109 of 229) of HER2− mBC patients had been recommended to undergo genetic testing by the MTB. Of these informed patients, 89.0% (97 of 109) underwent genetic testing, of which 11.6% (11 of 95) had a germline BRCA mutation (gBRCAmut) and were eligible for PARPi treatment. In multivariate analysis, younger age (p-value: 0.0007), hormone receptor positive (HR+)/HER2− subtype (p-value < 0.0001) and positive family history for breast and ovarian cancer (p-value: 0.0001) were significantly associated with the performance of genetic counseling. Conclusions: The present study demonstrated low genetic counseling rates of HER2− mBC patients, especially in individuals without specific risk factors for hereditary breast cancer. Informed patients showed a high willingness to undergo genetic testing. Genetic testing revealed targetable mutations in over 10% of tested patients. Full article

The toxicity of radioactive metals arises from both chemical toxicity and radiotoxicity. ²¹⁰Pb(II) is a long-lived radionuclide in the decay chain of natural uranium series ²³⁸U and exhibits extremely high toxicity. Both ²¹⁰Pb(II) and Pb(II) are widely present in natural water bodies. However, their combined toxicity remains unclear. Based on this, this study used zebrafish embryos as model organisms to investigate developmental toxicity, behavioral toxicity, and thyroid disruption effects, through single and combined exposure to Pb(II) (0, 1, 10, 100 μg/L) and ²¹⁰Pb(II) (0, 100, 1000 Bq/L) for 120 h by comparing the radiotoxicity of ²¹⁰Pb(II) with the chemical toxicity of Pb(II) and further exploring their combined effects. The results showed that following exposure to different environmental concentrations of Pb(II) and environmental activity levels of ²¹⁰Pb(II), exposure to Pb(II) alone caused an increase in the malformation rate of zebrafish embryos, a decrease in locomotor activity, and significant upregulation of thyroid-related genes, including thyroid hormone receptor beta (TRβ) and corticotropin-releasing hormone (CRH) in the larvae. Exposure to ²¹⁰Pb(II) alone had no significant effects on zebrafish embryos. Notably, compared with the individual exposure groups, the toxic effects in the combined exposure group of Pb(II) and ²¹⁰Pb(II) were further significantly enhanced. Furthermore, correlation analysis indicated a positive correlation between malformations in zebrafish embryos and the expression of key genes in the hypothalamic–pituitary–thyroid (HPT) axis. These findings suggest that under combined exposure, the chemical toxicity of Pb(II) plays a dominant role, while the radioactive component ²¹⁰Pb(II) exerts a synergistic amplification effect. This study provides important scientific evidence for improving the environmental risk assessment of radioactive metals. Full article

Bilirubin, historically recognized solely as a waste product of heme catabolism, has recently gained attention for its potential protective role in the cardiovascular system. Experimental and clinical studies suggest that bilirubin exhibits potent antioxidant, anti-inflammatory, anti-apoptotic, and cytoprotective properties that may protect the heart against oxidative stress, ischemia–reperfusion injury, and the progression of cardiovascular diseases, such as heart failure. As an endogenous hormone, bilirubin activates peroxisome proliferator-activated receptor-α (PPARα), a nuclear receptor that controls energy balance and lipid metabolism. Moderately elevated circulating bilirubin levels have been associated with a reduced risk of coronary artery disease, heart failure, and myocardial infarction; however, the mechanisms underlying bilirubin’s protective effects remain incompletely understood. Conversely, the gut microbiota’s metabolism of bilirubin to urobilin is detrimental, given urobilin’s association with cardiometabolic dysfunction. The therapeutic potential of bilirubin in the management of cardiovascular disease is becoming increasingly apparent, supported by preclinical research and emerging technologies that enhance bilirubin delivery via nanoparticles and methods to elevate plasma bilirubin levels. Collectively, these scientific advancements position bilirubin as a promising, biologically plausible endogenous therapeutic for the prevention and treatment of heart disease. Full article

Background: Breast cancer (BC) is a leading cause of cancer-related mortality worldwide and a major public health concern in Mexico. Regulatory variants in KRAS, particularly within the 3′UTR and intronic regions, may influence gene expression through microRNA binding and transcriptional regulation. Methods: Five regulatory single-nucleotide variants (SNVs) in KRAS (rs12228277, rs1137196, rs8720, rs12587, and rs12245) were genotyped in BC patients and cancer-free controls. Associations were evaluated using odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for age, alcohol, and tobacco use. Multiple testing was corrected using the Benjamini–Hochberg false discovery rate (FDR). Linkage disequilibrium (LD), multilocus combinations, and in silico functional analyses were also performed. Results: Variants rs12228277, rs1137196, rs8720, and rs12245 showed significant genotype-level associations with BC susceptibility, all remaining significant after FDR correction (pFDR < 0.05). No clinicopathological associations remained significant after correction in single-variant analyses. Multilocus analysis identified specific high-risk combinations (e.g., involving rs12228277, rs1137196, and rs8720) associated with increased BC susceptibility. At the nominal level, these combinations showed associations with clinicopathological features, including hormone receptor–positive status (PR and ER), proliferation markers, and Luminal B subtype; however, none remained significant after FDR correction. LD analysis indicated weak linkage among variants. In silico analyses suggested potential regulatory effects on microRNA binding and KRAS expression. Conclusions: Regulatory variants in KRAS are associated with BC susceptibility through independent effects and potential combinatorial patterns. These findings support the relevance of non-coding variation in cancer risk and warrant further functional and replication studies. Full article

Background/Objectives: Ovarian function suppression (OFS) is part of endocrine therapy treatment for high-risk premenopausal women with hormone receptor-positive (HR+) breast cancer (BC). Incomplete OFS may occur and compromise treatment efficacy. Methods: We conducted a retrospective single-center cohort study of premenopausal patients with HR + BC treated with OFS therapy at the Centre des maladies du sein (CMS) of the CHU de Québec (Québec, Canada). Ovarian function suppression failure was defined as either biochemical failure (estradiol (E2) levels within the premenopausal range according to local immunoassays used) or clinical failure (return of menstrual bleeding). Patients’ characteristics, treatment specifics and side effects, timing and type of OFS failure, recurrence, and mortality were analyzed. Results: Among 208 included patients, 17 (8.2%) experienced at least one episode of OFS failure during a median follow-up of 62.6 months. Most failures occurred early, with 76.2% occurring within the first year of treatment. No significant differences were observed between patients with and without OFS failure regarding age, body mass index (BMI), or prior chemotherapy exposure. Patients with OFS failure had a significantly younger age at first pregnancy and higher rates of active smoking. No BC recurrence or death occurred among patients with OFS failure. Treatment-related side effects were common, and 23.0% of OFS regimens were discontinued due to adverse effects. Conclusions: In this study, OFS failure occurred in fewer than 10% of premenopausal patients. Younger age at first pregnancy and active smoking may be associated with OFS failure, but further data are needed to validate these exploratory associations. These findings reinforce the need for larger prospective studies to better assess OFS failure and develop standardized monitoring strategies to optimize treatment efficacy. Full article

The protective effect of physical activity on breast cancer recurrence may be mediated changes in by sex hormone levels. In this study, we examined the association between habitual physical activity and estrogen and androgen plasma levels in postmenopausal women with localised breast cancer. We conducted a cross-sectional study among 47 postmenopausal women who were breast cancer survivors with estrogen receptor-positive tumours (enrolled at the Medical Oncology Department of University Hospital Dr. Peset, Valencia, Spain). Habitual physical activity was assessed using the International Physical Activity Questionnaire (IPAQ), and a weighted estimate of total physical activity per week (MET∙min∙wk⁻¹) was calculated. Total plasma levels of estrone, 17β-estradiol, progesterone, androstenedione, testosterone, and dehydroepiandrosterone-sulphate (DHEA-sulphate) were measured. Bivariate analyses by the Spearman correlation test were done between physical activity and each hormone concentration. Multivariate analyses (linear regression) using concentration of each hormone as the dependent variable and physical activity, age, marital status, BMI, Charlson Comorbidity Index, tumour stage, previous radiotherapy, or previous chemotherapy as predictor variables. Estrone concentration was positively and significantly correlated with BMI (ρ = 0.332, p = 0.022), but no other correlations were found between BMI and the other hormone concentrations, nor were concentrations of any hormone associated with age or Charlson Comorbidity Index (p > 0.05 in all cases). Physical activity was significantly and inversely correlated with estrone concentration (ρ = −0.308; p = 0.035). Linear regression analysis confirmed a statistically significant association between estrone concentration and BMI and physical activity, after adjusting for all potential confounders (for BMI: standardised β coefficient = 0.407; non-standardised β coefficient = 1.054; t = 2.898; p = 0.006; 95% CI for non-standardised beta: 0.318- to 1.790; for physical activity: standardised β coefficient = −0.300; non-standardised β coefficient = −0.005; t = −2.135; p = 0.039; 95% CI for non-standardised beta: −0.010- to 0.000). The relationship between estrone concentration and physical activity may be further explored as a biomarker for evaluating the protective effect of physical activity against breast cancer recurrence in women receiving anti-estrogen therapies. Full article