ER (Estrogen receptor)

Our findings demonstrate that Prickle1 loss in the myometrium results in a UL phenotype characterized by altered collagen expression, excessive extracellular matrix (ECM) deposition, aberrant smooth muscle cell organization, increased Esr1 and Pgr expression, and dysregulated Wnt/PCP signaling. This novel mouse model serves as a valuable preclinical tool for understanding UL pathogenesis and developing future pharmacotherapies.

Adjusting treatment strategies based on BMI across different menopausal statuses and tumor subtypes could improve outcome for patients with ER-positive/PR-positive tumors.

The absence of calcifications, non-mass lesions, lack of vascularity, and the non-enlarged scope can lead to misdiagnosis of DCIS and DCISM. Understanding the CEUS and clinicopathologic features of DCISM lesions may alert clinicians to the possibility of microinvasion and guide appropriate management.

Additionally, patients with HER2 and TN primary breast tumors exhibited the shortest DFS. Based on these findings, the study recommends the implementation of biomarker testing for recurrent breast cancers as a valuable strategy to inform and guide decisions regarding the selection of rescue chemotherapy, endocrine therapy, and targeted therapy.

We tested whether this HR dysfunction could indeed be exploited using PARP inhibition and found that talazoparib treatment produced a durable growth suppression in vitro and in multiple ILC xenografts in vivo...ILC are rarely associated with biomarkers of HR deficiency, and as such patients are rarely eligible for treatment with PARP inhibitors. Our work suggests ILC present with a previously unappreciated form of HR dysfunction, linked to ILC-specific genomic activity of ER and MDC1, which imparts sensitivity to PARP inhibition.

These systems have good prospects in improving the bioavailability of PTX, enhancing tumor targeting, reducing toxicity, controlling drug release, and reverse tumor multidrug resistance (MDR). This review provides valuable insights into the clinical development and application of PTX-targeted NDDS in the treatment of TNBC.

No abstract available

We delve into the specifics of PARPi, androgen receptor (AR) inhibitors, Cancer stem cells (CSCs), PI3K/ Protein Kinase B (AKT)/ mammalian target of rapamycin (mTOR), the transforming growth factor-beta (TGF-β), Ntoch, Wnt/β-catenin, hedgehog (Hh) pathway inhibitors, Epigenetic target-mediated drug delivery, ADCs, immune checkpoint inhibitors (ICIs)and novel immunotherapeutic solutions, contextualizing TNBC within current treatment paradigms. By elucidating the mechanisms of these drugs and their prospective clinical applications, we aim to shed light on the challenges and underscore the beacon of hope that translational research and innovative therapies represent for the oncology field.

P3, N=812, Recruiting, Hoffmann-La Roche | Trial completion date: Sep 2032 --> Dec 2030 | Trial primary completion date: Aug 2026 --> Mar 2027

P3, N=500, Recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Jun 2026 --> Apr 2028 | Trial primary completion date: Jun 2025 --> Apr 2027

Our results support the possibility to omit radiotherapy after breast-conserving surgery in a well-defined subgroup of women aged ≥ 65 years with low-risk, ER-positive, pT1N0 breast cancer receiving adjuvant endocrine therapy.

Our study suggests differential tamoxifen benefit by menopausal status. Improved long-term endocrine therapy prediction in premenopausal patients is needed and could involve molecular markers because standard tumor characteristics cannot predict benefit beyond 10 years.

P2, N=333, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Mar 2025 | Trial primary completion date: Oct 2024 --> Mar 2025

CDK4/6 inhibitors such as palbociclib block cell cycle progression and improve outcomes for many ER+/HER2- breast cancer patients...Understanding the molecular mechanisms that allow treated tumor cells to evade arrest is critical for identifying targets of future therapies. Ultimately, we seek to further SPCA as a tool of precision medicine, targeting treatments by individual tumors, and extending this computational framework to interpret other cyclical biological processes represented by high-dimensional data.

P=N/A, N=329, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed

P2, N=60, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Dec 2024 --> Jun 2025

P2, N=200, Recruiting, Oana Danciu | Trial completion date: Dec 2027 --> Aug 2029 | Trial primary completion date: Dec 2024 --> Aug 2028

Knockdown of NSRP1 reduces CDK4/6i (palbociclib) sensitivity of MCF7 cells while overexpression of NSRP1 sensitizes MCF7-PalR cells towards palbociclib treatment...In addition, including NSD2 exon 2 elevates NSD2 protein expression to activate the IFN signaling pathway. This study unveils the critical role of NSRP1 in regulating the IFN signaling pathway and the CDK4/6i resistance, which could be a promising biomarker for predicting therapy response.

Young patients with breast cancer have a lower 5-year survival than the UK average for all ages, and patients in this single-centre study with ER+ tumours appeared to have better short-term but similar longer-term outcomes compared to ER- breast cancer.

Consequently, 4-OHE2-HSA may serve as a novel molecular target for potential cancer therapeutics. Furthermore, autoantibodies against 4-OHE2-HSA could serve as a potential biomarker for early detection of BC.

P2, N=106, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed

This review underscores the need for careful histologic and immunohistochemical evaluation to differentiate HAC from other malignancies, particularly in the breast region. Given the rare and the potential aggressive nature of HAC, early and accurate diagnosis is crucial for guiding appropriate therapeutic strategies and improving patient outcomes.

Cytoplasmic CAIX was independently associated with poor prognosis in ER- BC. Gene expression profiles shed light on the pathways and genes associated with hypoxia in ER- BC. In node-negative patients, SPNS2 was of particular interest.

We found that Basal like breast cancer, HER2+, and stage 3 increase the chance of EpCAM positivity. It seems that EPCAM positive cancer has more chance for recurrence and metastasis.

Dural metastases can occur as a subsequent event in patients with poorly controlled extensive bone metastases, with the frontoparietal area being the most commonly involved site. Radiotherapeutic strategy is highly influenced by the associated metastatic volume of DM, and radiotherapy was found to improve prognosis in these patients.

These results support a potential role of the palbociclib-letrozole combination as treatment for hormone receptor-positive advanced/recurrent endometrial cancer. Based on these encouraging results, phase III evaluation of letrozole combined with a CDK4/6 inhibitor is planned.

Harmaline was found to promote apoptosis and inhibit cell proliferation, invasion, and migration in TNBC cells by targeting the inhibition of c-Myc. It also induced the re-expression of the ER, PR, and HER-2 genes, as well as the ER and PR proteins.

Drug sensitivity analysis, molecular docking, and cell experiments consistently demonstrated positive correlations between F2R expression and sensitivity to dasatinib. This study underscores the potential of F2R as a valuable biomarker in BC, providing insights into the molecular mechanisms underlying tumorigenesis.

The final diagnosis was leiomyoma coexisting with low-grade ESS, classified as International Federation of Gynecology and Obstetrics (FIGO) stage IB. The patient received no further treatment and remains disease-free after 45 months.

These findings highlight the potential roles of LIF and avβ3 in IUA prevention strategies and provide important insights for future clinical interventions. Tubal mucosal cells can not only grow in the endometrial cell microenvironment, but also the tolerance of tubal mucosal cells can be improved when they are co-cultured.

P1, N=24, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P1/2 --> P1 | Trial completion date: Mar 2025 --> Jul 2025

SLBC is a rare morphologic pattern of invasive breast carcinoma that mimics metastatic serous gynaecologic carcinoma, a potential diagnostic pitfall. SLBC are heterogeneous with respect to grade, receptor profile, and oncogenic driver alterations, without specific genetic underpinnings identified. Additional studies are warranted to further evaluate the clinical behaviour of these tumours.

In conclusion, GZFL combination treatment could increase the clinical effectiveness rate of EMs patients, and reduce the serum level of carbohydrate antigen 125, estradiol, matrix metalloproteinases, pain scores, and the diameter of the ectopic cyst. The potential mechanism might be linked to the modulation of hormone receptors and inflammation.

This research uncovers the possible mechanisms of CS in CH treatment, offering new avenues for future studies.

P3, N=240, Recruiting, MedSIR | Not yet recruiting --> Recruiting | Initiation date: Sep 2024 --> Dec 2024

P2, N=160, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | Trial completion date: Feb 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

While anti-estrogens that degrade ERα (fulvestrant) or block estrogen production (aromatase inhibitors) have improved patient outcomes, clinically important challenges remain related to drug administration, limited bioavailability, lack of brain exposure, and acquired resistance due to ESR1 mutations...Combining imlunestrant with abemaciclib (CDK4/6 inhibitor), alpelisib (PI3K inhibitor), or everolimus (mTOR inhibitor) further enhanced tumor growth inhibition, regardless of ESR1 mutational status. In an ER+ breast cancer intracranial tumor model, imlunestrant prolonged survival compared to vehicle or alternative SERD therapies. Together, these finding support the potential of imlunestrant to degrade ERα and suppress the growth of ESR1 wildtype and mutant breast cancer, including brain metastatic tumors.

In addition, an attenuated response to LNS8801 is observed in a common germline coding variant in human GPER. These findings support ongoing human cancer trials with LNS8801 and suggest that the germline GPER genotype may serve as a predictive biomarker of therapeutic response.

LicA targets SREBP1, a central regulator of lipogenesis and immune response, reducing pro-tumorigenic aberrations in lipid homeostasis and inflammation. It is a promising non-endocrine candidate for BC prevention.

This study elucidates the immunosuppressive role of ER signaling in breast cancer, highlighting a complex interplay between cancer, stromal, and immune cells and reveals potential approaches to enhance immunogenicity in HR+ breast cancer. These findings offer crucial insights into immune evasion in breast cancer and identify strategies to enhance T cell abundance.

All hybrid ligands are antagonists of estrogen receptor alpha and agonists of the melatonin MT1 receptor with variable potencies. Several drug conjugates including the (CH2)4-linked analogues 4a and 16a and the (CH2)6-linked compound 16c showed higher potency to inhibit cell viability than the combination of melatonin and tamoxifen on at least one cancer cell line including MCF-7, MDA-MB-231, and HT-1080.

These tools take into consideration the histopathologic parameters and immunohistochemistry (IHC) biomarkers data for estrogen receptor/progesterone (ER/PR), human epidermal growth factor receptor 2 (HER2), and Ki67...No significance was noted across different prediction tools. The findings are suggestive that ME predictive scores are more relevant and informative compared to other online tools and with an additional AR IHC expression analysis the recurrence prediction might prove to be beneficial and feasible to many deprived BC patients.