Estrogen Receptor Positive Breast Cancer

P=N/A, N=797, Completed, BeamWorks Inc.

P=N/A, N=40, Active, not recruiting, Varian, a Siemens Healthineers Company | Recruiting --> Active, not recruiting | Trial completion date: Oct 2025 --> Dec 2026

P=N/A, N=150, Not yet recruiting, University of Salamanca

P1, N=470, Recruiting, SystImmune Inc. | N=260 --> 470 | Trial primary completion date: Dec 2025 --> Dec 2026

Higher CTC signature ITH was associated with increased Oncotype DX risk and higher overall grade. These findings highlight the value of our CTC signature in disease progression and the role of ITH on recurrence risk.

To test this hypothesis, we treated MCF-7 and T47D ER-positive breast cancer cells with 17-β-estradiol (E2), either alone or in combination with selective ERα antagonist AZD9496, selective ERβ antagonist PHTPP, DNA methyltransferase (DNMT) inhibitor RG108, and selective ER degrader Fulvestrant (Ful). RG108 strengthened UV-C-induced pyroptosis, and Ful reversed the inhibitory effects of E2 on UV-C-induced pyroptosis of MCF-7 and T47D cells. Taken together, our study suggests that E2 down-regulated GSDME expression in ERα-positive breast cancer by promoting GSDME promoter methylation, and inhibited UV-C-induced pyroptosis.

Fulvestrant, a selective estrogen receptor degrader (SERD) that antagonizes and degrades ER simultaneously, has demonstrated activity in ER+/HER2- breast cancers the ability to overcome endocrine resistance. These data support the clinical utility of ZN-c5 as monotherapy and as a combination therapy for patients with ER+/HER2- breast cancers. While encouraging plasma exposure and tolerability have been observed for ZN-c5 in patients, further studies are needed to optimize its therapeutic efficacy.

P1, N=18, Recruiting, Shanghai Juncell Therapeutics | Trial primary completion date: Nov 2025 --> Nov 2026

P1, N=22, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

GR-driven gene programmes are selectively activated in in vivo models of ERα-positive breast cancer during fasting, and GR knockout hinders the anti-tumour effects of fasting combined with tamoxifen...Additionally, tumours collected after the fasting-mimicking diet showed an inverse correlation of GR activation with proliferation markers, providing clinical confirmation of our observations in animal models. Our results indicate that GR activation has a pivotal role in the ability of fasting to enhance endocrine therapy activity in breast cancer and suggest that corticosteroid administration should be evaluated as an adjuvant to endocrine therapy in this setting.

As cytoplasmic localization occurs in ~11% of ER+ patients, it represents a contributor to MLH1 dysregulation. Incorporating cytoplasmic MLH1 localization into diagnostics could guide the use of CDK4/6 inhibitors in this hard-to-treat subset.