P3, N=315, Active, not recruiting, AstraZeneca | Trial completion date: Nov 2027 --> Sep 2028

P3, N=300, Not yet recruiting, Genentech, Inc.

P=N/A, N=200, Recruiting, Institut Claudius Regaud | Trial completion date: Feb 2026 --> Feb 2028 | Trial primary completion date: Feb 2026 --> Feb 2028

We observed similar ET-response rates in two large phase III trials. Postmenopausal patients (mostly receiving AI) had higher ET-response rates compared to younger patients. However, young patients with GnRH+AI had ET-response rates comparable to postmenopausal patients, suggesting that therapy rather than biology accounts for the difference. Combining ET-response and gene expression assessment could help more luminal eBC patients avoid chemotherapy.

P2, N=96, Not yet recruiting, University Health Network, Toronto

P3, N=1000, Recruiting, Olema Pharmaceuticals, Inc.

Functional assays in BRCA cells were performed to evaluate the effects of MYO1B on cell proliferation, apoptosis, and sensitivity to tamoxifen and palbociclib. Mechanistically, MYO1B activated the Pi3k-AKT signaling pathway. Our study suggests that MYO1B promotes the progression of BRCA and may serve as a new target for overcoming endocrine therapy resistance.

Combining HER3-DXd with an ATR inhibitor could benefit HER3+/HR+ BC patients with both endocrine-sensitive and -resistant diseases.

Interestingly, the molecular docking analyses indicated β-sitosterol to have stronger affinity to ERα, ERβ, IGF1R and VEGFR2 than that of their known inhibitors (tamoxifen, diarylpropionitrile, linsitinib and sorafenib, respectively). Finally, molecular dynamics simulations analyses confirmed strong molecular interactions of β-sitosterol with VEGFR2 and ERβ. Taken together, the findings highlight potential of phytoconstituents of Pterospermum acerifolium, especially β-sitosterol, kaempferol and luteolin, for clinical management of breast cancer and its metastasis to the bone.

Additionally, low vimentin and enhanced E-cadherin expression lead to downregulation of core EMT regulators, including SNAIL1 and ZEB1. In conclusion, TQ showed potential chemomodulatory effects on TAM against TNBC by reducing the expression of EMT-associated markers.

The combination of tamoxifen and E. bulbosa ethanol extract significantly reduced COX-2 levels in DMBA-induced breast cancer models. These results suggest the potential of this combination as an effective adjuvant therapy. Further studies are needed to confirm the underlying molecular mechanisms and to evaluate its toxicity profile.

These findings establish a mechanistic link between hormonal signaling, p53 allelic status, and m6A-dependent post-transcriptional regulation. Although further in vivo validation is required, disruption of the ALKBH5-REG1A axis may contribute to heterogeneous endometrial responses to tamoxifen, thereby providing a conceptual framework for biomarker-oriented investigation.