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Background Clinical trials have shown the efficacy of adding CDK4/6 inhibitors to standard endocrine therapy in hormone receptor (HR)-positive, human epidermal growth factor receptor II (HER2)-negative high-risk early breast cancer. Materials and methods HR+ /HER2− early breast cancers were retrieved from cancer registry. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) among trial-defined high-risk patients, as well as the impact of adjuvant chemotherapy. Results Among 2758 registered cases, 511 and 1207 patients met MonarchE (M) and NATALEE (N) high-risk criteria, respectively. OS was 94.8% for M-high/N-high, 96.8% for M-low/N-high, 90.7% for M-high/N-low, and 98.9% for M-low/N-low patients, with a hazard ratio (HR) of 2.3 and 2.8 for M-high and N-high, respectively. For RFS, chemotherapy reduced recurrence risk in M-high patients (HR: 0.24) but showed no benefit for N-high patients overall, except for stage III N-high cases (HR: 0.2). Conclusion Adjuvant chemotherapy significantly reduced recurrence risk in M-high patients with early breast cancer. Further stratification of M-low/N-high patients is needed to guide tailored chemotherapy approaches alongside CDK4/6 inhibition.

Background Optimal treatment strategies for early-stage human epidermal growth factor receptor 2 (HER2) positive breast cancer with low estrogen receptor (ER) expression (1–9%) remain unclear. While endocrine therapy (ET) is standard for ER-positive disease, its benefit in ER-low tumors, particularly with concurrent HER2 overexpression, is less established. Methods We conducted a retrospective cohort study using Taiwan’s national cancer registry (TCR), identifying 10,408 patients with HER2-positive early breast cancer diagnosed between 2011 and 2019. Of these, 1436 (15.5%) had low ER positivity. Patients were stratified by ER level (1–9% vs. ≥ 10%) and ET use. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free survival (RFS) were evaluated via Kaplan–Meier and Cox regression analyses. Progesterone receptor (PR) status was also assessed. Results Adjuvant ET significantly improved OS, BCSS, and RFS in both ER subgroups (all p < 0.05). In ER-low patients, ET was associated with improved OS (8.2 ± 0.1 years vs. 7.9 ± 0.1 years, 90.2% vs. 85.6%, p = 0.008), BCSS (8.4 ± 0.1 years vs. 8.2 ± 0.1 years, 93.9% vs. 89.7%, p = 0.005), and RFS (8.8 ± 0.1 years vs. 8.8 ± 0.1 years, 91.2% vs. 88.2%, p = 0.032) up to 10 years of follow-up. On multivariate analysis, PR positivity—not ER level—was an independent predictor of improved outcomes. Notably, PR-positive, ER-low patients had better OS with ET (92.1% vs. 86.7%, p = 0.022). Further subgroup analysis also showed improved OS, BCSS and RFS outcomes for those receiving longer ET duration (> 60 months) or for non-pathological complete response (pCR) patients. Conclusion Adjuvant ET provides significant survival benefits in HER2-positive early breast cancer with low ER expression, particularly in PR-positive tumors. Despite this, 41.9% of eligible ER-low patients did not receive ET, highlighting a treatment gap. PR status may guide ET decisions, supporting individualized treatment approaches. Adjuvant ET also showed survival benefits in non-pCR patients with longer duration (> 60 months) associated with better survival outcomes. Although the survival benefit of adjuvant ET appeared greater in patients without pCR, the benefit in the pCR group could not be quantified due to the limited sample size. Importantly, our findings do not suggest withholding ET in patients achieving pCR.

The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. Furthermore, multiple sclerosis diagnostic criteria have been developed primarily using data from North America and western Europe. Although some diagnoses mistaken for multiple sclerosis are common regardless of location, a comprehensive approach to the differential diagnosis of multiple sclerosis in Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific regions requires special consideration of diseases that are prevalent in those locations. A collaborative effort has therefore assessed global differences in multiple sclerosis differential diagnoses and proposed recommendations for evaluating patients with suspected multiple sclerosis in regions beyond North America and western Europe.

Gingele and colleagues point out that a relative afferent pupillary deficit was absent in 43 people (83%) of 52 people previously diagnosed with optic neuritis in their multiple sclerosis cohort. According to the figure in the Position Paper,1 only a diagnosis of possible optic neuritis or exclusion of optic neuritis can be made from the Gingele and colleagues’ cohort, because of the retrospective nature. [...]to move forward on the suggestion to broaden the diagnostic role of paraclinical tests to reach a diagnosis of definite optic neuritis, cohorts should be reassessed prospectively using our criteria; and such validation study might also consider the inclusion of optical coherence tomography,2 which was not mentioned in either letter. AP declares grant support for remyelination trials in multiple sclerosis to the Amsterdam University Medicam Centre, Department of Neurology, MS Centre (for the RESTORE trial), and University College London (for the RECOVER trial); funding for a trial from Fight for Sight (nimodipine in optic neuritis trial); royalties or licenses from Up-to-Date (Wolters Kluver) on a book chapter; speaker fees from the Heidelberg Academy; participation on advisory boards for SC Zeiss Optical Coherence Tomography Angiorgaphy Angi-Network and the SC Novartis Optical Coherence Tomography in Multiple Sclerosis study; leadership roles for a governing board for International Multiple Sclerosis Visual System Consortium (until December, 2022) and Chairman of European Reference Network for rare Eye Diseases Neuro-ophthalmology (until October, 2020); is a board member of National Dutch Neuro-ophthalmology Association; received equipment from Optical Coherence Tomography Angiorgaphy and Zeiss (Plex Elite); and provided medical writing support to Novartis.