Outcomes were excellent regardless of chemotherapy or ET, suggesting limited incremental benefit from treatment intensification.

Postoperatively, he received adjuvant stereotactic radiosurgery (30-35 Gy in five fractions) to the resection cavity and was transitioned from tamoxifen to trastuzumab deruxtecan (T-DXd) for improved CNS-directed systemic therapy. Surveillance imaging at 6 months demonstrated no intracranial recurrence, and systemic restaging showed no extracranial disease progression. This case highlights the importance of prompt neuroimaging for new neurological symptoms in male breast cancer patients and supports a multimodal strategy, including surgical resection, focal radiation, and CNS-penetrant HER2-targeted therapy, for achieving durable intracranial control in select patients with isolated brain metastasis.

Although anti-estrogen treatments such as tamoxifen have significantly improved treatment outcomes, but their prolonged use is associated with therapeutic resistance and adverse effects...The multistep screening identified HIT 1 compound with a superior docking score (-13.901 kcal/mol) as compared to standard drug raloxifene (-12.136 kcal/mol), as well as favourable pharmacokinetic properties and enhanced MM-GBSA binding free energies...In addition, DFT calculations supported its electronic stability and bio-feasibility through analysing its HOMO-LUMO energy gap. These results suggest that the HIT 1 molecule serves as a promising scaffold for the development of a novel ERα modulator with potential to suppress ERα-mediated BC progression and angiogenesis.

Compounds 19 and 21 underscored significant human ERα inhibition in contrast to tamoxifen and bazedoxifene...Moreover, pharmacokinetics and DFT analysis ensured drug-likeness and bio-feasibility of promising molecules. Finally, based on interaction-analysis, bio-assay findings, and 3D-QSAR mapping, an overall structure-activity correlation was established for future-optimization and lead-development of indole - 4,5-dihydroisoxazole hybrids against ER+ BC.

P2, N=240, Active, not recruiting, AstraZeneca | Trial completion date: Mar 2026 --> Jun 2027

P3, N=150, Not yet recruiting, AstraZeneca

Notably, in human cell lines HER2∆16 expression is elevated upon acquired resistance to HER2-targeted therapy and can sensitize cells to the ER-antagonist tamoxifen. Overall, these findings offer valuable insights into the role of HER2∆16 in promoting luminal cell identity and estrogen receptor positivity in breast cancer, providing a useful platform to model HER2+/ER+ disease.

P=N/A, N=0, Available, Genentech, Inc.

Our study uncovers a molecular mechanism by which 4-OHT promotes TNBC stemness via the NRP-1/CAPN2/β-catenin signaling cascade. Targeting NRP-1 may serve as a valuable strategy to improve TAM efficacy in ERα-re-expressing TNBC.

Tamoxifen-inducible, endothelial-specific deletion of VEGF receptor 2 (Vegfr2), the principal mediator of VEGF signaling, induced marked vascular regression in the epiphysis and led to growth plate cartilage expansion following epiphyseal ischemia...Moreover, epiphyseal vascular regression exacerbated bone mineral density loss in an ovariectomy-induced mouse model of osteoporosis. Collectively, these findings advance our understanding of angiogenic-osteogenic coupling in adulthood and provide a mechanistic framework for the vulnerability of the femoral head and neck to fractures in the elderly.

P2, N=96, Not yet recruiting, University Health Network, Toronto | Initiation date: Apr 2026 --> Jul 2026

P3, N=1556, Suspended, Alliance for Clinical Trials in Oncology | N=1156 --> 1556