Estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer is the most common type of breast cancer, and endocrine therapy remains the cornerstone of treatment. This narrative review summarizes the biology of mutations in the ligand-binding domain of the estrogen receptor (ER), the utility of circulating tumor DNA (ctDNA) for detecting these alterations, and the evidence supporting emerging therapies for ESR1-mutant metastatic disease to provide clinicians with a practical, evidence-based framework for managing patients with the disease. Mutations in the ligand-binding domain of ESR1, such as Y537S and D538G, lock the receptor in a constitutively active conformation, increasing resistance to aromatase inhibitors and variably affecting sensitivity to selective ER degraders (SERDs). These mutations can be detected non-invasively by longitudinal ctDNA next-generation sequencing, often before radiographic progression is evident, although questions remain regarding optimal assay sensitivity, clonal heterogeneity, and monitoring intervals. Elacestrant, the first oral SERD approved for ESR1-mutant disease, improved progression-free survival in the phase III EMERALD trial and subsequent trials of oral SERDs, and the proteolysis-targeting chimera vepdegestrant (EMBER-3, SERENA-6, and VERITAC-2) provides further supporting evidence. Other complete ER antagonists and covalent antagonists remain in clinical trials. ESR1 mutation testing and treatment adaptation according to ctDNA are now part of the precision management of ER+/HER2− breast cancer, but more prospective research is required for the best sequencing and monitoring strategies.

Lymphoepithelioma-like carcinoma (LELC) of the urinary bladder is a rare variant of urothelial carcinoma accounting for less than 1% of all bladder malignancies, characterized by syncytially arranged tumor cells within a dense lymphoplasmacytic stroma and consistent Epstein–Barr virus (EBV) negativity. We report a male patient in his sixth decade presenting with painless gross hematuria. Cystoscopy revealed an endoscopically unresectable lateral wall bladder mass, confirmed on biopsy as muscle-invasive high-grade urothelial carcinoma, LELC variant (cT2N0M0), with moderate (2+) GATA3 positivity and negative EBER-ISH. Following three cycles of neoadjuvant cisplatin-gemcitabine chemotherapy, restaging imaging demonstrated complete clinical response (ycT0N0M0). Radical cystectomy with extended bilateral pelvic lymph node dissection and ileal conduit urinary diversion was performed. Final histopathological examination confirmed complete pathological response (ypT0N0), with fibrosis and inflammatory changes only, negative surgical margins (R0), and 10-15 tumor-free lymph nodes retrieved. This case highlights the exceptional chemosensitivity of bladder LELC to platinum-based neoadjuvant chemotherapy and underscores the necessity of proceeding with radical cystectomy despite radiological complete response.

Aplastic anemia is a rare hematologic disorder characterized by bone marrow failure and pancytopenia. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for eligible patients. In selected cases, radiation-based conditioning strategies, such as total nodal irradiation (TNI), may be incorporated into transplant protocols to enhance immunosuppression and facilitate donor cell engraftment. We present a 30-year-old male patient diagnosed with aplastic anemia in 2021 who underwent allogeneic HSCT from a matched sibling donor in 2023. Salvage transplantation was planned in 2024 due to persistent marrow dysfunction. As part of the conditioning regimen, TNI was administered. TNI was delivered on November 8, 2024 (day-4 prior to transplantation) as a single fraction of 7.5 Gy using volumetric-modulated arc therapy. This case demonstrates the feasibility of TNI as part of a conditioning regimen for salvage HSCT in patients with aplastic anemia.