Estrogen Receptor Positive Breast Cancer

P=N/A, N=68, Active, not recruiting, Mayo Clinic | Trial completion date: Mar 2026 --> Mar 2028 | Trial primary completion date: Mar 2026 --> Mar 2028

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

Routine assessment of ESR1 mutations using liquid biopsy should be integrated into clinical practice to enable dynamic, molecularly guided treatment optimization. The expanding arsenal of ER-targeted therapies supports personalized sequencing strategies that move beyond rigid temporal cutoffs and improve outcomes in ET resistant disease.

We investigated whether DHED could prevent side effects associated with the aromatase inhibitor letrozole in a primate model of aging...Here, we show that a brain-selective estrogen therapy administered orally via the prodrug DHED substantially increases estrogen levels in the marmoset brain without affecting the periphery and normalizes impairments in working memory, hippocampal neuronal excitability and sleep induced by aromatase inhibition. These findings in a translational primate model represent a significant advance for women's health by positioning DHED as a non-invasive, safe and efficient novel hormone therapy to improve quality of life of women with ER+ breast cancers.

Functional perturbation experiments in ER+ breast cancer cells showed that TGF-β stimulation enhanced invasive behavior, whereas knockdown of MMP1 or COL7A1 attenuated epithelial-mesenchymal transition (EMT) marker expression and invasion. Together, our study delineates RBP-associated regulatory programs linking cellular state transitions to invasive signaling in ER+ breast cancer.

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.

Conversely, in ER-positive tumors, apocrine morphology was associated with increased proliferation, enhanced immune-related signaling, and greater genomic instability. In conclusion, apocrine morphology represents an ER-dependent biological state with distinct prognostic and molecular implications.

P1, N=90, Recruiting, Cogent Biosciences, Inc. | Not yet recruiting --> Recruiting | Initiation date: Feb 2026 --> Jun 2026

P3, N=1978, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Initiation date: Jul 2026 --> Feb 2027

This study confirms that 3-hydroxybenz[a]anthracene exhibits estrogen-like activity in vitro and can influence malignant biological behaviors of breast cancer cells by regulating relevant signaling pathways. These findings provide experimental evidence for further evaluating the endocrine-disrupting effects and breast cancer risks associated with such environmental pollutants.

Finally, we showed that combining PPRHs targeting SF3B1 or SRSF1 with Tamoxifen or 4-hydroxytamoxifen reduced MCF-7 cell viability in an additive or synergistic manner, respectively. Our results indicate that SF3B1 and SRSF1 participate in the generation of different ERα splicing variants and their inhibition by PPRHs could have therapeutic potential in the treatment of estrogen receptor positive breast tumors.