tamoxifen

The cardiomyocyte-specific, tamoxifen-inducible TOP2B transgenic mice exhibited pathophysiological features consistent with doxorubicin-induced cardiotoxicity, even without exposure to anthracyclines. Our findings reveal a novel role for TOP2B in AIC, demonstrating that its upregulation disrupts SMYD1 function in cardiomyocytes, contributing to cardiotoxicity. This study also highlights the therapeutic potential of targeting TOP2B using ASO for preventing AIC in cancer patients, offering new insights into cardioprotective strategies.

Integrating machine learning with XAI and Bayesian approaches effectively identified key predictors of mortality in tamoxifen-treated breast cancer patients. However, marked heterogeneity in model performance across subgroups highlights the critical need for external validation and careful evaluation of algorithmic fairness before clinical implementation.

Following tamoxifen induction, blood blister-like lesions developed on the tail, ear, and paw in 86.9% (53/61) of mice harboring at least one Pik3caH1047R allele, whereas no lesions were observed in mice lacking the mutant allele (0/13, P < 0.0001)...Together, these findings demonstrate that PIK3CA activation initiates highly penetrant vascular malformations, whereas p53 loss promotes their rare neoplastic transformation. This model provides mechanistic and translational insight into how benign PIK3CA-mutant vascular malformations may progress toward vascular malignancy and offers a platform for studying biomarkers and therapeutic strategies to prevent this transition.

EET (with tamoxifen monotherapy, LHRH agonist plus tamoxifen, or LHRH agonist plus aromatase inhibitor), irrespective of the duration of EET, measured at study baseline (defined as the first day of the sixth year after the initiation of adjuvant ET)...In this cohort study, a lower estimated risk with EET use was observed across all surrogate breast cancer subtypes. However, the lower estimated risk was greatest among patients with luminal A-like disease, a finding that warrants confirmation in larger, prospective cohorts.

These findings indicate that ATP attenuates tamoxifen-induced retinal toxicity by supporting mitochondrial energy balance and redox homeostasis. Accordingly, ATP administration may represent a promising protective approach for reducing retinal injury associated with long-term tamoxifen therapy.

POH also inhibited the growth of Tamoxifen- and Fulvestrant-resistant BC cells...Finally, in silico screening using MD simulations identified venetoclax and nystatin as potential ANT2 pore binders. Both compounds reduced ERα levels in ERα-positive BC cells and increased lipid droplet formation in Fulvestrant-resistant cells. These findings highlight ANT2 as a druggable target against endocrine-resistant BC.

Background: Oral progestogens, including megestrol acetate (MA) and medroxyprogesterone acetate (MPA), have largely been superseded by aromatase inhibitors, tamoxifen, and selective oestrogen receptor degraders (SERDs) in oestrogen receptor-positive (ER-positive) metastatic breast cancer. While prior exposure to CDK4/6 inhibitors was associated with shorter PFS, patients without liver metastases appeared to derive the greatest benefit. These findings support a role for oral progestogens in selected patients who have exhausted standard therapeutic options.

Both 1 and 2 mg of (Z)-endoxifen significantly reduced MBD to a degree comparable to the established 20 mg dose of tamoxifen. The 1 mg dosage of (Z)-endoxifen indicated superior tolerability. Future studies are necessary to confirm impact on breast cancer incidence.

For premenopausal women with ER-positive early breast cancer, even if chemotherapy or tamoxifen are given, OFS significantly reduces the 15-year risk of recurrence and death.

Compound juvenile Pdgfrα-CreER;Ext1f/f and Fgf18-CreER;Ext1f/f mice were injected with tamoxifen and monitored for tumor development over time...Analyses also showed that the developing osteochondromas in the Pdgfrα;Ext1 mutants displayed strong expression of cartilage proteins and abundant pSMAD1 and pSMAD2 proteins that mediate pro-chondrogenic BMP/TGFβ signals. The data provide new evidence that perichondrium progenitors, and more specifically inner layer cells delineated by Pdgfrα expression, initiate osteochondroma formation, being redirected into an ectopic chondrogenic program by Ext1 loss and deficiency of its vital function.

Preliminary results further indicated that combining IVM with tamoxifen enhanced its antiproliferative effects in endocrine-resistant breast cancer cells, suggesting a potential role in overcoming drug resistance...This inhibition was accompanied by a decrease in phosphorylated SMAD2 (pSMAD2) within the TGF-β pathway, while levels of SMAD4-a factor associated with favorable prognosis in endocrine resistance-were maintained. Collectively, these findings highlight IVM's potential as a repurposed therapeutic agent, with the dual capacity to prevent endocrine resistance in ER⁺ breast cancer and to enhance anti-hormonal therapies in resistant cases.

P2, N=140, Recruiting, Andrea DeCensi | N=95 --> 140