Anastrozole (ANZ) is a commonly used aromatase inhibitor in the treatment of hormone-dependent breast cancer. Despite its toxicity profile reported in different studies, the neurotoxic effects against this drug have not been explored yet. The present study was aimed at investigating the neurotoxic effects of ANZ in Sprague Dawley rats using comprehensive biochemical, molecular and histopathological analysis. Rats were divided into control and ANZ treated (0.1, 0.2 and 0.5 mg/ kg) doses. It was found that ANZ intoxication promoted the gene expression of NLRP3, PYCARD, CASP1, IL1-β, IL18, TXNIP, SNCA, and LRRK2 while suppressing the expression of PARK2, PINK1, PARK7 and UCHL1 in dose dependent manner. Moreover, ANZ exposure significantly reduced the antioxidant defense systems as shown by reduction in the activities of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR), glutathione-peroxidase (GPx) and heme oxygenase-1 (HO-1) coupled with elevated levels of malondialdehyde (MDA) and reactive oxygen species (ROS). Similarly, ANZ administration showed marked reductions in the levels of BDNF, NGF, GDNF PSD-95, and synaptophysin while increasing the levels of NF-κB, COX-2, TNF-α, IL-1β, and IL-6. Nonetheless, ANZ exposure provoked the levels of Caspase-9, Bax, and Caspase-3 while inhibiting the levels of Bcl-2. Histological examination confirmed the dose-dependent neuronal degeneration such as vacuolization, pyknosis and structural disorganization. Collectively, these results showed that ANZ causes significant neurotoxicity due to oxidative stress, inflammation, and apoptosis resulting in neuronal survival and function dysfunction. This study shows the importance of careful therapeutic use of ANZ and laid down the foundation for further research on the neurological safety profile of ANZ.

Breast cancer (BC) represents a serious threat to public health worldwide, especially for women. Anastrozole (ATZ) is recognized as a therapeutic candidate for treating BC. However, its poor solubility and bioavailability result in low efficacy. This study set out to improve ATZ's ability to manage BC by developing a nasal spray formulation of ATZ-loaded transbilosome (ALT) that would increase ATZ's sustainability, bioavailability, targeting, and efficacy. Design Expert software was used to make different ALT formulations, and the optimum one was chosen. The optimal ALT formulation was then evaluated in vivo using an Ehrlich-induced BC mouse model to assess its efficacy, bioavailability, targeting, and safety. The optimized ALT formulation consists of phospholipid (271.62 mg), Span 60 (24.69 mg), and sodium deoxycholate (18.19 mg). Optimized ALT outperformed free ATZ by 77% in sustainability, 7.88 times in bioavailability, 11.62 times in permeation, and 5.52 times in targeting. Tumor volume, mortality rates, and levels of the biomarkers Ca-15-3 and Ca-27.29 were all significantly lower in the nasal ALT group compared to the disease group by 99.08%, 23.33%, 97.76%, and 98.73%, respectively. The nasal ALT formulation is considered safe because it did not adversely affect kidney or liver functions. In conclusion, the nasal ALT formulation shows potential as a therapy for managing BC.

Ribociclib adds progression-free survival and overall survival benefit in combination with endocrine therapy for first-line treatment of advanced HR+ HER2- breast cancer; however, it comes with a risk of hepatotoxicity. There is guidance for monitoring liver function and holding the medication if hepatotoxicity arises. However, there is minimal guidance for management if withholding the medication alone is insufficient. We present a case of a woman with de novo metastatic HR+ HER2- breast cancer who developed grade 2 AST and ALT elevation after two cycles of ribociclib and anastrozole, which progressed over several weeks to Grade 4 hepatotoxicity despite holding the medication. Extensive evaluation revealed drug-induced liver injury from ribociclib as the cause. Ultimately, a long course of corticosteroids was initiated with remarkable response and resolution of transaminitis. An empiric trial of corticosteroids should be considered for patients with severe ongoing hepatotoxicity from CDK4/6 inhibitors despite cessation of the drug.

A perimenopausal woman presented with a slowly enlarging right axillary mass initially suspected to be a sebaceous cyst. An incisional biopsy revealed high-grade invasive ductal carcinoma arising from accessory axillary breast tissue. Imaging showed no orthotopic breast lesion and staging was cT1N0M0. She underwent axillary lumpectomy and sentinel lymph node biopsy, confirming pT1bN0M0 invasive carcinoma. Adjuvant therapy included whole breast radiation, hormonal therapy with anastrozole and goserelin. At 2 years, she remains disease-free. This case highlights the diagnostic challenge of accessory axillary breast cancer (AABC), a rare entity often missed on routine imaging. Early recognition and application of standard breast cancer treatment protocols can result in excellent outcomes. Clinicians should maintain a high index of suspicion for AABC in axillary masses, especially in patients with no primary breast findings on imaging to ensure timely diagnosis and appropriate management.

Anastrozole and abemaciclib are clinically recommended in combination for the treatment of advanced breast cancer. However, the potential drug-drug interaction between them remains poorly characterized, posing a potential risk for altered drug exposure and toxicity. This study aimed to systematically investigate the effect of anastrozole on the metabolism and pharmacokinetics of abemaciclib. Using a combined in vitro and in vivo approach, we characterized this interaction via UPLC-MS/MS analysis of abemaciclib and its major metabolites (M2 and M20). In vitro enzymatic assays demonstrated that anastrozole significantly inhibits the metabolism of abemaciclib. Consistent with these findings, in vivo studies in female Sprague-Dawley rats showed that 7-day pretreatment with anastrozole prior to abemaciclib administration substantially decreased abemaciclib clearance, resulting in markedly increased systemic exposure (AUC0-t, AUC0-∞, and C max). Given that abemaciclib is predominantly metabolized by CYP3A4, we further examined whether genetic polymorphisms in this enzyme influence the observed interaction. Our results revealed that CYP3A4 genetic polymorphisms significantly modulate the inhibitory potency of anastrozole. These findings indicate that anastrozole acts as a CYP3A4 inhibitor, altering abemaciclib disposition in a genotype-dependent manner. This study highlights a clinically significant drug interaction with potential toxicological implications and provides a mechanistic basis for genotype-guided therapy in patients receiving this combination regimen.

The association between long-term aromatase inhibitor (AI) use and osteoporosis remains controversial. Clarifying this relationship is critical for optimizing the safety of breast cancer survivors. This study collected publicly available data from Q1 2005 through Q1 2025 in the FAERS database. Three types of AIs were included in the study, and adverse events were restricted to the " Primary Suspect". The narrow definition of "osteoporosis/osteopenia" in the MedDRA Standard query (SMQ) was used for case screening. Additionally, to investigate adverse outcomes related to osteoporosis, we used vertebral compression fractures-the most typical fracture type in osteoporosis-to explore potential severe outcomes that may occur following drug administration. Disproportionality analysis utilized reporting odds ratio (ROR), PRR, IC, and EBGM. Positive signals were defined only when meeting criteria for all four algorithms. Subgroup and Weibull distribution analyses were performed to assess onset time. A total of 19,590 AIs related adverse event reports were extracted during the monitoring period, of which 665 were osteoporosis-related events, and the patients were mainly women aged 65 years and older. At the system-organ class (SOC) level, musculoskeletal system showed a strongest positive signal. At the SMQ level, anastrozole and letrozole showed significant positive signals associated with osteoporosis. In contrast, exemestane did not reach statistical significance. Similarly, positive disproportionality analysis signals for vertebral compression fracture as an adverse event were identified for anastrozole and letrozole, whereas negative signals were observed for exemestane. TTO analysis showed that exemestane-induced osteoporosis events followed an early failure-type curve with the median time to onset of about 245 days. Analysis reveals distinct bone safety profiles. Anastrozole and letrozole demonstrated significant associations with osteoporosis, whereas exemestane did not, suggesting a superior safety profile. These findings offer reference for clinicians regarding individualized drug selection for patients at high skeletal risk.

The manufacture and distribution of illicit drugs in the Republic of Korea are an increasing problem. We aimed to develop a rapid and reliable simultaneous analytical method for monitoring the illegal presence of anabolic androgenic steroids (AAS) in foods and drugs. Forty-five AAS compounds were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in accordance with international standards. Liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) has enabled the determination of representative fragment ion patterns. The validated method was applied to 95 real samples, including 11 foods, 40 dietary supplements, and 44 counterfeit drugs. The overall detection rate was 38.9%, with the highest rate observed in counterfeit drugs (81.8%), followed by dietary supplements (2.5%), whereas no AAS were detected in foods. When classified by formulation, injectables showed the highest detection rate (100.0%), followed by liquids (78.6%), tablets (58.3%), powders (20.0%), and capsules (3.3%). Frequently detected compounds included testosterone-17-propionate (0.001-119, 850.0 μg/g), testosterone-17-isocaproate (0.002-1442.7 μg/g), and nandrolone decanoate (0.01-120,023.0 μg/g). Anastrozole and exemestane, which are not currently included as LC-MS/MS target compounds, were also identified through LC-QTOF/MS. Furthermore, LC-QTOF/MS results revealed the presence of nonsteroidal compounds, including phosphodiesterase-5 inhibitors and weight-loss compounds, indicating potential health risks associated with the combined pharmacological effects of these substances. The analytical method developed in this study can be effectively used for both screening and quantification and offers practical applicability to regulatory monitoring and enhancement of public health protection.

Background/Objectives: Previous studies have suggested that lifestyle intervention (LSI) therapies involving diet and exercise can modulate DNA methylation; however, whether this occurs in severely obese hypogonadal men undergoing weight loss from diet and exercise remains unclear. Methods: In this study, we investigated the effects of weight loss from diet and exercise on global DNA methylation as well as on the mRNA expression of specific demethylation enzymes, DNMT1, DNMT3A, and DNMT3B-in peripheral blood mononuclear cells (PBMCs) and DNA methylation markers in DNA of severely obese hypogonadal men. This is a secondary analysis of samples of severely obese (body mass index of ≥35 kg/m[2]) hypogonadal men undergoing weight loss from diet and exercise in addition to an aromatase inhibitor (anastrozole) or placebo for a total of 12 months. Results: LSI therapy significantly reduced global DNA methylation and 5-methylcytosine (5-mC) levels, decreased DNMT1, DNMT3A, and DNMT3B (p < 0.05) mRNA levels and markedly decreased CEBPα, FTO, and PPARγ mRNA expression. The reduction in global methylation was independent of aromatase inhibitor use. Conclusions: In summary, our findings suggest that LSI induces epigenetic modifications in leukocytes, possibly through the regulation of DNMT gene expression. Future studies are warranted to clarify the mechanistic pathways linking lifestyle-induced epigenetic alterations to metabolic health outcomes.

Cutaneous metastatic carcinoma is a malignant tumor that originates outside the skin. Studies have found that the most common primary tumor in female patients with cutaneous metastatic carcinoma is breast cancer. Cutaneous metastatic carcinoma spreads to the adjacent skin through blood vessels, lymphatics, or interstitial spaces. It forms ulcerative or nodular lesions. Carcinoma en cuirasse is characterized by extensive induration and sclerosis of the skin, resembling armor, and is a rare form of cutaneous metastatic carcinoma.

Comparative analysis of protein-ligand interactomes is crucial for understanding binding specificity, drug efficacy, and the impact of structural changes such as mutations. However, comparing the full spectrum of non-covalent interactions between different complexes often requires manual data extraction and complex workflows. We developed juProt, an open-source web application, to automate and streamline the comparative analysis of the complete protein-ligand interactome. juProt is developed in Julia using the Genie.jl framework and integrates the Protein-Ligand Interaction Profiler (PLIP) for comprehensive interaction detection. Users can either upload local PDB structures or automatically fetch files directly from the RCSB PDB using PDB IDs. The application detects and compares the full range of non-covalent interactions, including Hydrogen Bonds, Hydrophobic Contacts, π-Stacking, Salt Bridges, and Water Bridges. It generates comparative outputs including quantitative metrics, fold-change calculations, and 2D spatial pocket projections to visually map the geometric distribution of interacting residues. Validation against standalone PLIP using 20 diverse protein-ligand complexes (experimental and docked) demonstrated 100% concordance across all supported interaction types. A case study on human aromatase and its inhibitors (Letrozole, Anastrozole) interacting with native and mutant forms showcased juProt's utility. The analysis revealed that the Met364Thr mutation significantly remodeled the hydrophobic core of the Letrozole binding site, a structural insight clearly illustrated by the comparative 2D spatial mapping. juProt offers a robust, user-friendly methodology for the comparative analysis of the complete protein-ligand interactome. By automating data retrieval, calculating quantitative fold-changes, and generating spatially explicit 2D pocket projections, it significantly lowers the barrier for comprehensive structural analysis without requiring specialized graphics software. The tool is freely available at juprot.info.