Explore the vast range of titles available.

Background Approximately 20–30% of patients with metastatic breast cancer (MBC) develop brain metastases (BM) over the course of their disease. It is critical to better understand risk factors and survival outcomes in these patients, including those treated in the modern treatment era. Methods We identified patients with MBC and BM diagnosed between 1997 and 2024 at our institution. Review of medical records was completed to identify key demographic, clinical, and survival characteristics. Results We identified 507 patients with MBC and BMs with the following subtypes: HR+/HER2- ( n  = 184, 36.3%), HER2+ ( n  = 197, 38.9%), and triple negative breast cancer (TNBC; n  = 126, 24.9%). Median real-world overall survival (rwOS) from the diagnosis of first BM to death was 21.6 months with the longest median rwOS in patients with HER2+ disease (31.0 months) vs. patients with HR+/HER2- (19.6 months) or TNBC (12.8 months) ( p  < 0.001). By date of BM diagnosis 1997–2014 vs. 2015–2024 (divided by ~ 50% of patients in each time period), patients with HER2+ and TNBC lived longer in the more modern cohort compared to prior years (HER2+: 41.2 vs. 26.2 months, p  = 0.002; TNBC: 14.9 vs. 7.0 p  = 0.020). There was no statistically significant difference for patients with HR+/HER2- disease (16.5 vs. 21.6, p  = 0.089). On multivariable analysis, HER2+ disease (HR 0.64, 95% CI 0.50–0.81, p  < 0.001), BM surgical resection (HR 0.67, 95% CI 0.51–0.87, p  = 0.002), and BM diagnosis after 2014 (HR 0.77, CI 0.63–0.95, p  = 0.015) were associated with longer survival. TNBC (HR 1.46, CI 1.12–1.89, p  = 0.004), having 6–10 BMs at baseline (HR 1.66, CI 1.14–2.42, p  = 0.009), extracranial MBC (HR 1.34 CI 1.02–1.76, p  = 0.034) and development of leptomeningeal disease (HR 1.41, CI 1.11–1.80, p  = 0.005) were associated with shorter survival. Conclusion In a cohort of > 500 patients with MBC BMs spanning > 25 years, median rwOS from the diagnosis of first BM was almost two years. Favorable factors included HER2+ disease, BM surgical resection, and diagnosis after 2014. Poor prognostic factors included TNBC, having 6–10 BMs, extracranial MBC, and development of LMD. Patients with HER2+ and TN MBC with BM had improved rwOS in a more modern cohort; this was not seen for HR+/HER2- patients, representing an area of ongoing unmet clinical need.

Background Zilovertamab is a humanized monoclonal antibody targeting ROR1, an onco-embryonic antigen expressed by malignant cells of a variety of solid tumors, including breast cancer. A prior phase 1 study showed that zilovertamab was well tolerated and effective in inhibiting ROR1-signaling, which leads to activation of ERK1/2 , NF-κB , and NRF2 target genes. This phase 1b study evaluated the safety and tolerability of zilovertamab with paclitaxel in patients with advanced breast cancer. Patients and methods Eligible patients had locally advanced, unresectable, or metastatic HER2 − breast cancer with Eastern Cooperative Group performance status of 0–2 and without prior taxane therapy in the advanced setting. Study treatment included 600 mg of zilovertamab administered intravenously (IV) on Days 1 and 15 of Cycle 1 and then Day 1 of each 28-day cycle along with paclitaxel weekly at 80 mg/m 2 IV. Results Study patients had received a median of 4 prior therapies (endocrine therapy + chemotherapy) for locally advanced, unresectable, or metastatic disease. No patient discontinued therapy due to toxicity ascribed to zilovertamab. Adverse events were consistent with the known safety profile of paclitaxel. Of 16 patients, 6 (38%) had a partial response, and 6/16 (38%) patients had stable disease as best tumor response. Conclusion The combination of zilovertamab and paclitaxel was safe and well tolerated in heavily pre-treated advanced breast cancer patients. Further evaluation of ROR1 targeting in breast cancer patients with zilovertamab is warranted. Trial Registration : NCT02776917. Registered on ClinicalTrials.gov on 05/17/2016.

Leishmaniasis is a spectrum of diseases caused by Leishmania species protozoa that is most common in warm climates, coinciding with impoverished regions. Visceral leishmaniasis is a potentially fatal disease in which parasites infect reticuloendothelial organs and cause progressive wasting and immunocompromise. Visceral leishmaniasis is a potentially fatal disease caused by the protozoon Leishmania donovani or L. infantum (Li). Although previous studies revealed that high lipid intake reduces parasite burdens in Leishmania donovani -infected mice, the specific contributions of dietary lipids to Li-associated pathogenesis are not known. To address this, we evaluated parasite growth, liver pathology, and transcriptomic signatures in Li-infected BALB/c mice fed either a control, high-fat, high-cholesterol, or high-fat–high-cholesterol diet. Using quantitative PCR (qPCR), we observed significantly reduced liver parasite burdens in mice fed the high-fat–high-cholesterol diet compared to mice fed the control diet. In contrast to the liver, parasite expansion occurred earlier in the spleens of mice fed the experimental diets. Histological examination revealed an intense inflammatory cell infiltrate in livers predominantly composed of neutrophils caused by the high-fat–high-cholesterol diet specifically. After 8 weeks of infection (12 weeks of diet), Illumina microarrays revealed significantly increased expression of transcripts belonging to immune- and angiogenesis-related pathways in livers of both uninfected and Li-infected mice fed the high-fat–high-cholesterol diet. These data suggest that increased fat and cholesterol intake prior to Li infection leads to a hepatic inflammatory environment and thus reduces the parasite burden in the liver. Defining inflammatory signatures as well as pathology in the liver may reveal opportunities to modify the therapeutic approach to Li infection. IMPORTANCE Leishmaniasis is a spectrum of diseases caused by Leishmania species protozoa that is most common in warm climates, coinciding with impoverished regions. Visceral leishmaniasis is a potentially fatal disease in which parasites infect reticuloendothelial organs and cause progressive wasting and immunocompromise. The distribution and demographics of visceral leishmaniasis have changed over recent years, coinciding with modernizing societies and the increased availability of Western diets rich in lipid content. We report here that increased dietary fat and cholesterol intake affected disease pathogenesis by increasing inflammation and reducing localized parasite burdens in the liver. These diet-induced changes in disease pathogenesis might explain in part the changing epidemiology of visceral leishmaniasis. A relationship between diet and inflammatory responses may occur in leishmaniasis and other microbial or immune-mediated diseases, possibly revealing opportunities to modify the therapeutic approach to microbial infections.