Purpose of review Immune checkpoint inhibitors (ICIs) are increasingly used in breast cancer, particularly in triple-negative breast cancer. This review summarizes the biologic rationale and emerging clinical evidence for time-of-day ICI administration and discusses its implications for breast cancer. Recent findings Circadian rhythms provide a biologic rationale for time-dependent immunotherapy efficacy. Several retrospective studies across multiple tumor types have suggested associations between earlier ICI administration and improved outcomes, although findings remain inconsistent. Breast cancer-specific data are expanding but remain heterogeneous, with signals varying by treatment setting, endpoint, timing definition, and tumor immune contexture. These findings suggest that treatment timing should be interpreted in the context of the broader treatment platform in which immunotherapy is delivered, including concomitant chemotherapy and supportive medications, as well as host circadian state and tumor immune contexture. An ongoing prospective study aims to integrate circadian, systemic immune, and tumor-based assessments to elucidate the biological and clinical relevance of treatment timing in breast cancer. Summary Current evidence does not establish an optimal infusion window for breast cancer treatment. Prospective studies integrating clinical outcomes with circadian, systemic immune, and tumor-based analyses are needed to determine whether treatment timing can be developed into a biologically informed strategy.
Purpose of review Despite maximal neoadjuvant chemoimmunotherapy, nearly 40% of early-stage triple-negative breast cancer (TNBC) patients fail to achieve pathological complete response, underscoring an urgent need for biomarkers capable of guiding treatment modulation. This review summarizes recent advances in tumor-infiltrating lymphocytes (TILs), circulating tumor DNA (ctDNA), and genomic signatures, exploring their potential integration into clinical decision-making. Recent findings TILs remain the most validated, cost-effective prognostic biomarker, although standardized scoring is still needed to overcome interobserver variability. ctDNA has emerged as a dynamic, real-time prognostic tool, with postneoadjuvant detection strongly predicting relapse and worse outcomes. Nonetheless, optimal sampling timing remains undefined. Genomic signatures, particularly TNBC-DX, provide standardized, reproducible prognostic information by integrating immune and proliferative gene expression. Emerging data suggest that combining these biomarkers may offer a complementary and synergistic effect. Summary Multibiomarker integration, supported by prospective validation and automated models, represents a promising approach to personalize treatment algorithms in early-stage TNBC, balancing efficacy and toxicity while guiding escalation and de-escalation strategies.
PURPOSE OF REVIEW:This review aims to provide a summary of the latest novelties in the field of paraneoplastic neurological syndromes (PNS), emphasizing relevant clinical updates on epidemiology, antibody discovery, and testing. RECENT FINDINGS:Population-based studies have provided estimates of PNS incidence in the United States and Europe. A wider availability of commercial and in-house antibody testing, together with the discovery of novel antibodies, was pinpointed as a possible reason for the progressive increase in PNS incidence observed in recent years. Updated diagnostic criteria for PNS diagnosis published in 2021 were validated in cohorts of adults and children, showing improved sensitivity and similar specificity compared to the 2004 criteria. Laboratory studies have highlighted the pitfalls of commercial and in-house assays for antibody detection, underscoring the importance of sample referral to reference centers for additional analyses in selected cases. Novel antibodies to intracellular and cell-surface antigens associated with paraneoplastic encephalitis (NIF, ZSCAN1, septin-7, PDE10A, CAMKV), cerebellar syndrome (e.g. TRIM46, TRIM9/67, SEZ6L2, RGS8, mGluR2), and brainstem encephalitis (KELCH11, LUZP4) were described and related to recurring cancer types, expanding the PNS spectrum. SUMMARY:The present review provides an update on PNS, including novel antibodies and phenotypes.
PURPOSE OF REVIEW:Liquid biopsy (LB) is rapidly transforming the management of hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (mBC). In this review, we discuss the most recent findings on circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), exploring their roles across the treatment continuum, from treatment selection to resistance monitoring. RECENT FINDINGS:ctDNA-based detection of actionable mutations - including ESR1 and PIK3CA - achieved regulatory validation as a primary predictive biomarker for treatment selection, supporting the approval of novel endocrine agents and targeted therapies in HR+/HER2- mBC. Serial ctDNA monitoring demonstrated the ability to intercept emerging resistance mechanisms ahead of radiological progression, opening a window for preemptive therapeutic adaptation. CTCs enumeration maintains robust independent prognostic value, with emerging evidence supporting its role in guiding treatment escalation and de-escalation decisions. Integrated multiparametric LB approaches combining CTCs and ctDNA are crucial to improve prognostic accuracy and clinical decision-making. SUMMARY:LB is progressively shifting from a research tool to a clinical decision-making instrument in HR+/HER2- mBC. Prospective interventional trials, methodological standardization, and integrated strategies are needed to fully translate its potential into improved patient outcomes.
PURPOSE OF REVIEW:Antibody-drug conjugates (ADCs) have rapidly advanced from later-line salvage therapy into first-line metastatic and curative perioperative settings. This review appraises recent practice-changing data that collectively redefined treatment standards across Human epidermal growth factor receptor 2 (HER2)-positive, triple-negative, and hormone receptor-positive/HER2-negative breast cancer. RECENT FINDINGS:Three trials, DESTINY-Breast09, DESTINY-Breast05, and DESTINY-Breast11, established the role of T-DXd across first-line metastatic and perioperative HER2-positive settings, with both early breast cancer indications receiving FDA approval in May 2026. In triple-negative disease, ASCENT-04/KEYNOTE-D19 established sacituzumab govitecan plus pembrolizumab as new first-line option for Programmed cell death ligand 1 (PD-L1)-positive metastatic TNBC. Meanwhile, TROPION-Breast02 had led to the approval of Datopotamab deruxtecan (Dato-DXd) for the first-line treatment of immunotherapy-ineligible patients with metastatic TNBC, whereas ASCENT-03 led to the NCCN incorporation of first-line sacituzumab govitecan for the same population. Multiple further neoadjuvant and adjuvant ADC trials are expected to further reshape treatment algorithms over the coming years. SUMMARY:ADCs now hold regulatory and guideline approval as preferred first-line options across all major breast cancer subtypes, in both the metastatic and curative perioperative settings. Proactive ILD surveillance is essential across all approved agents. Remaining challenges include sequencing among topoisomerase I inhibitor-payload ADCs and awaiting mature survival readouts from perioperative trials.
