tamoxifen

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.

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.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, such as abemaciclib, ribociclib, and palbociclib, are used in combination with ET as a standard of care first-line option in HR+, HER2- advanced disease to improve survival outcomes...Abemaciclib has also been shown to be effective when combined with a variety of ET options, including aromatase inhibitors, tamoxifen, fulvestrant, imlunestrant, or as monotherapy, and has shown efficacy regardless of prior CDK4/6 inhibitor exposure, ESR1 or PI3K pathway mutational status, menopausal status, and in both endocrine-sensitive and endocrine-resistant breast cancer. Importantly, the safety profile of abemaciclib has been consistent across trials and allows the administration of the drug over long periods of time when needed, particularly if dose-reduction strategies are employed. Together, the data summarized in this publication help inform clinical decision making regarding the role of abemaciclib in the treatment of patients with both early and metastatic HR+, HER2- breast cancer.

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

PDZK1 functions as a regulator of HER2 stability and may serve as a potential biomarker and therapeutic target in HER2-positive breast cancer. Pharmacological upregulation of PDZK1 may represent a promising combinatorial therapeutic strategy for overcoming therapeutic resistance in breast cancer.

In the tamoxifen resistance context, PAK1 inhibition induced activation of the pro-apoptotic protein BAD and triggered apoptosis while proliferation-related kinases were suppressed in the estrogen-deprived model. Our findings position PAK1 as a mediator of resistance to endocrine therapies suggesting that targeting PAK1 may present a novel strategy to overcome endocrine therapy resistance in ER+ breast cancer.