Breast cancer is a highly heterogeneous malignancy, characterized by diverse genetic, epigenetic, and phenotypic variations, as well as by metabolic reprogramming and oxidative stress. Lipid peroxidation bioactive product 4-hydroxynonenal (4-HNE) plays a significant role in the development and progression of cancer. In this study, we quantified circulating 4-HNE-modified proteins and performed comprehensive untargeted metabolomic profiling of the patients’ plasma using LC-ESI-QTOF-MS and GC-EI-QMS, aiming to investigate systemic metabolic pathways associated with oxidative damage in breast cancer. Significantly elevated levels of 4-HNE-modified proteins were detected in breast cancer patients compared to healthy controls, accompanied by distinct metabolomic signatures enriched in lipid metabolism. Several metabolites, including specific long-chain fatty acids, exhibited significant correlations with circulating 4-HNE-modified proteins, suggesting an interaction between lipid peroxidation-driven protein modification and breast cancer-associated metabolic reprogramming. Overall, this study provides evidence of associations between systemic 4-HNE-mediated protein modification and altered metabolic profiles in breast cancer, highlighting oxidative stress–related metabolites as potential biomarkers and pointing to redox-metabolic crosstalk in breast cancer patients.

Introduction Neratinib is approved in Europe as extended adjuvant therapy in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-positive (HER2+) early-stage breast cancer (EBC) who completed adjuvant trastuzumab-based therapy within 1 year. Real-world data are necessary to define the role of neratinib in the evolving treatment landscape. Methods NEAR was a retrospective, observational study evaluating treatment patterns, safety and effectiveness of neratinib during a European early access program (EAP). Eligible patients had HER2+ EBC and received neratinib between August 2017 and December 2020. Data were extracted from medical records up to July 2022. The primary endpoint was the patient demographic and clinical profile. Results Among 108 eligible patients, most had HR+ disease (n = 92) and a high risk of recurrence (defined as stage II–III or node-positive disease, or non-pathological complete response after neoadjuvant therapy; n = 87); 74 were treated as per the neratinib European label. Trastuzumab plus pertuzumab and trastuzumab alone were the most common anti-HER2+ adjuvant therapies (9.3% and 88.4% of patients, respectively). Median duration of neratinib treatment was 12.3 months. Diarrhoea was the most common adverse event (58.3%). Prophylactic anti-diarrhoeal therapy reduced the occurrence of grade ≥ 3 diarrhoea (4.3% versus 13.2% without prophylaxis) and neratinib discontinuation (22.2% versus 35.7%, respectively). Exploratory invasive disease-free survival rates were 93.3% at 24 months and 89.9% at 36 months, with no central nervous system events. Conclusion These results provide additional data supporting the safety and exploratory effectiveness of neratinib in the EAP, reflecting real-world clinical practice. ClinicalTrials.gov Identifier NCT05599334 (31 October 2022, retrospectively registered).

Background and Objective Dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab combined with taxane-based chemotherapy (Cht) has been the standard first-line treatment for HER2-positive metastatic breast cancer (mBC) for years, due to the impressive results of the CLEOPATRA study. Real-world (RW) studies have become critical for assessing treatment effectiveness and safety in real-life circumstances. The aim of this study was to analyze the treatment outcomes of first-line therapy for HER2-positive mBC in RW clinical practice, specifically focusing on the use of maintenance endocrine therapy (ET) in hormone receptor positive (HR-positive) patients. Methods This retrospective analysis included 106 HER2-positive mBC patients treated with trastuzumab and pertuzumab combined with taxane-based Cht from October 2015 to December 2020 at the University Hospital Centre Zagreb. Results At a median follow-up of 30 months, median progression-free survival (PFS) was 25 months for the total population (95% confidence interval [CI] 16 - not analyzed). Patients with de novo mBC had longer median PFS than patients with recurrent disease (not reached vs. 18 months; hazard ratio 1.99; 95% CI 0.69–3.64, p<0.022). Age, hormone receptor positivity, visceral involvement, number of Cht cycles and previous adjuvant trastuzumab did not impact PFS. Most HR-positive patients (N=55, 88.7%) received maintenance ET after induction Cht. Conclusion This retrospective study provides additional data on patient characteristics, treatment and outcomes of RW HER2-positive mBC patients treated with pertuzumab and trastuzumab as first-line therapy. In our institution, maintenance ET after induction Cht has become standard clinical practice.

Uvod: Smrtnost sepse je visoka usprkos antimikrobnim lijekovima, stoga se ispituju imunomodulatorni lijekovi, između ostalih i statini. Cilj: Pokazati imaju li bolesnici prethodno liječeni statinima lakši klinički oblik i manju smrtnost sepse. Ustroj: Retrospektivno kohortno, opservacijsko istraživanje, usporedba prethodno liječenih i prethodno neliječenih statinima. Ispitanici: Sepsa iz opće populacije, bakterijski izolat iz hemokultura, dob ≥ 50 god. Rezultati: Uključeno 899 bolesnika, 116 (12.9%) prethodno liječenih statinima. Bez statistički značajnih razlika u izraženosti parametara sustavnog upalnog odgovora. Medijan SOFA zbroja u prethodno liječenih statinima iznosio je 2.0 kao i u skupini prethodno neliječenih (p=0.117). Ukupna smrtnost 9.2%, prethodno liječeni 6.0%, prethodno neliječeni 9.7%, (p=0.231). Nema razlike u 28-dnevnoj smrtnosti (log-rank test, p=0.693). Zaključak: Nema statistički značajne razlike u težini kliničke slike kao ni u smrtnosti sepse između bolesnika prethodno liječenih i prethodno neliječenih statinima.