In the phase 3 DESTINY-Breast05 study (NCT04622319) of T-DXd vs. T-DM1 in patients with residual invasive HER2+BC after neoadjuvant treatment (NAT), T-DXd demonstrated statistically significant and clinically meaningful improvement vs T-DM1 in the primary endpoint of invasive disease-free survival (IDFS) and the key secondary endpoint of disease-free survival (DFS; Geyer, ESMO 2025). ∼80% of patients had invasive residual disease in the axillary lymph nodes, 93% received adjuvant radiotherapy (56% concurrent [n = 918]; 37% sequential [n = 605]), and 79%received dual HER2-targeted NAT. Safety was generally manageable with no new safety signals. Here we report additional efficacy and safety data from the DESTINY-Breast05interim analysis. Patients with residual invasive HER2+ BC following NAT consisting of anti-HER2 therapy and taxane-based chemotherapy and at high risk for recurrence (cT4, N0-3, M0 or cT1-3, N2-3, M0 at presentation prior to NAT, or cT1-3, N0-1, M0, with axillary node-positive disease [ypN1-3] following NAT)were randomized 1:1 to T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg once every 3 weeks for 14 cycles. All patients receiving adjuvant radiotherapy (RT) were required to have serial chest computed tomography (CT) scans; details to be presented. RT could be administered concurrently with study therapy or prior to initiating study therapy (sequential). Patients receiving sequential therapy had an additional CT scan at the end of the RT. At data cutoff (July 2, 2025), 1635 patients were randomized to T-DXd (n = 818) or T-DM1 (n = 817). Median treatment duration was similar in both arms; more than 70% of patients in both arms received 14 cycles of study therapy. Efficacy results in clinically relevant subgroups will be presented. Adjudicated drug-related interstitial lung disease(ILD) and investigator-reported radiation pneumonitis by timing of adjuvant RT are summarized in the Table. Adjudicated drug-related ILD occurred in 9.6% of patients who received T-DXd; most ILD events were grade 1 or 2, and 0.2% had grade 5 events. No notable differences were observed based on adjuvant RT timing. Incidence of investigator-reported radiation pneumonitis was similar in both arms (31.4% with T-DXd and 30.5% with T-DM1), with no grade ≥3 events and being grade 1. The additional analyses further characterize the positive benefit of T-DXd over T-DM1 in the post-neoadjuvant HER2+ BC residual disease setting, supporting T-DXd as a potential new standard-of-care in this setting. Timing of adjuvant RT did not impact incidence of adjudicated drug-related ILD with T-DXd. Additional results will be presented. S. Loibl, Y. Park, Z. Shao, C. Huang, C. H. Barrios, J. Abraham, A. Prat, N. Niikura, M. Untch, S. Im, W. Li, H. Li, Y. Wang, H. Yao, S. Kim, E. Mathias, J. Petschauer, W. Lu, H. Abdel-Monem, C. E. Geyer Jr.. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with high-risk human epidermal growth factor receptor 2-positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy: Interim analysis of DESTINY-Breast05 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF6-01.
To evaluate whether distinct subtypes of hypertensive disorders of pregnancy (HDP), chronic hypertension (CH), pregnancy-specific hypertensive disorders (PSHD), and superimposed preeclampsia (CH + PE), are associated with differential neonatal outcomes in very preterm infants, independent of gestational age and perinatal confounders. We conducted a multicenter retrospective cohort study using prospectively collected data from the Brazilian Neonatal Research Network, including infants with birthweights 401–1500 g and gestational age 22 + 0 to 32 + 6 weeks (2013–2020). Infants were classified according to maternal hypertensive status. Primary outcomes included major neonatal morbidities and in-hospital mortality. Associations were assessed using Poisson regression with robust variance, adjusting for gestational age, birthweight, sex, antenatal corticosteroids, and perinatal variables. Analyses were stratified by gestational age (≤ 28 and > 28 weeks). Among 9,689 infants, 4,011 (41.4
BACKGROUND AND AIMS:The Val122Ile ATTR Amyloidosis has traditionally been linked to cardiac manifestations. Recent studies suggest that neuropathy may be relevant. In this study, we characterized its peripheral nerve manifestations in depth. METHODS:This was a national, multicenter, observational, retrospective study. Patients underwent careful clinical and neurophysiological evaluation. We excluded those with alternative etiologies. RESULTS:We identified 246 Val122Ile carriers, including 240 heterozygous, 4 homozygous, and 2 compound heterozygous. Gender distribution was similar. Age of onset: 19-89 years, mean 53 ± 17. Self-reported ethnicity: White (26.7%), Black (17.3%), and Mixed (Pardo) (56.0%). Birthplaces spanned all Brazilian regions, mainly the Northeast. Among heterozygotes, 52 of 122 (42.6%) were symptomatic. Carpal tunnel syndrome (CTS) preceded polyneuropathy and/or cardiomyopathy in 69.2%. The most frequent onset manifestations, excluding CTS, were cardiomyopathy (52.9%), neuropathy (37.3%), and mixed phenotype (9.8%). Age of onset: 29-86 years (mean: 64.9 years). During follow-up, 14/27 cardiac patients developed neuropathy, and 8/19 neurologic patients developed cardiomyopathy, significantly increasing the mixed phenotype from 9.8% to 52.9%. Most patients with neuropathy presented with sensory or sensory and motor disease (62.2%), followed by small fiber neuropathy (32.4%), and isolated dysautonomia (5.4%). INTERPRETATION:Neuropathy is underrecognized in Val122Ile ATTR Amyloidosis, is frequent at disease onset, may be the sole manifestation, and may occur in White persons. CTS frequently preceded neuropathy, usually an axonal polyneuropathy, although atypical patterns were observed. This variant clusters in the Northeast region of Brazil.
The molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) impact transmission, clinical presentation, and treatment. Contemporary data on the molecular epidemiology of MRSA causing healthcare-associated (HA) infections in Latin America are scarce. In this study, we aimed to assess the molecular epidemiology, virulence genes, and antimicrobial susceptibility of MRSA bloodstream infections (BSI) isolates from Brazil. A multicenter, prospective study in 14 Brazilian hospitals was conducted from August/2022 to August/2023. MRSA isolates recovered from HA-BSIs were sent to a central laboratory for whole-genome sequencing (WGS) and antimicrobial susceptibility testing. Of 255 S. aureus, 66 (25.9
