Abstract 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.
Abstract 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.
Abstract 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.
Abstract Background: Breast cancer is the most common cancer among women in India, particularly among urban women, yet awareness and early detection remain inadequate. Addressing this gap requires reliable, culturally appropriate tools to measure awareness levels and to promote targeted interventions. With the growing influence of digital media, social platforms offer a powerful channel for health communication. This study aimed to validate a breast cancer knowledge, attitude, and practice (KAP) scale specifically designed for social media-active urban Indian women. Methods: A cross-sectional study was conducted among a sample of women aged 18 years and above from the Delhi-National Capital Region. The 542 completed questionnaires were analyzed using confirmatory factor analysis (CFA) and reliability tests to validate the scale. The 36-item instrument assessed three domains: knowledge (risk factors, symptoms, and screening practices), attitude, and preventive practices. Content validity was established through expert evaluation, construct validity through CFA, and internal consistency through Cronbach’s alpha. Results: The CFA results demonstrated a good model fit. All items exhibited satisfactory factor loadings, with composite reliability values exceeding 0.70 and average variance extracted (AVE) values above 0.50, confirming convergent validity. Discriminant validity was also achieved as the AVE square roots were greater than inter-construct correlations. The overall Cronbach’s alpha of 0.87 indicated high reliability. Conclusion: The study provides a psychometrically tested tool to assess awareness (knowledge, attitude and practice) of breast cancer among digitally connected urban women. It can be used to identify knowledge gaps and evaluate the effectiveness of awareness campaigns.
Abstract Background: To evaluate the prognostic impact of perineural invasion (PNI) on oncological outcomes in oral cavity carcinoma patients. Methods: Chart review of 781 patients undergoing surgery for oral cavity carcinoma between 2013 to 2021 was done. All patients underwent surgery (per primum/post neoadjuvant chemotherapy) followed by adjuvant treatment as per histopathological report. Results: There were 653 male patients (83%) and the median age of the cohort was 48 years. Six hundred and thirty-two (80.8%) patients had locally advanced stage (III/IV). Three hundred and forty (44%) patients had PNI reported. PNI positivity correlated with higher pT stage, pN stage, overall stage and poor differentiation. Median follow-up was 51 months. At last follow-up, 571 patients (73%) were alive, of which 527 were disease free. Incidence of distant metastasis was significantly higher in patients having PNI (25% versus 13%, P = 0.001). On univariate analysis, patients with PNI-positive disease had significantly worse 5-year disease-free survival (DFS) (56% versus 68%, P = 0.001), locoregional control (LRC) (62% versus 72%, P = 0.001), and overall survival (OS) (57% versus 75%, P = 0.001) as compared to patients with PNI-negative disease. On multivariate analysis, PNI was significant factor only for OS ( P = 0.05), not for DFS ( P = 0.152) or LRC ( P = 0.174). For PNI-positive cohort, patients with perinodal extension had poor OS ( P = 0.01). Conclusion: PNI-positive disease had poor outcomes despite aggressive multimodality treatment. PNI positivity correlated with higher pT stage, pN stage, overall stage and poor differentiation. PNI may be considered an independent prognostic factor for OS in oral cavity cancers and should be evaluated further in a randomized controlled setting. Added presence of perinodal extension defines poor outcomes. Sub-classification of PNI may be tested for determining impact on outcomes.
