ER negative

P1, N=45, Recruiting, George T. Budd | Trial completion date: Sep 2024 --> Mar 2025 | Trial primary completion date: May 2024 --> Nov 2024

P=N/A, N=72, Active, not recruiting, University of Birmingham | Recruiting --> Active, not recruiting | N=150 --> 72

P1/2, N=188, Recruiting, Cancer Research UK | N=114 --> 188 | Trial completion date: Sep 2025 --> Jun 2027 | Trial primary completion date: Sep 2025 --> Jun 2027

P2, N=25, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Mar 2024 --> Dec 2026 | Trial primary completion date: Mar 2024 --> Dec 2026

In invasive lobular carcinoma, GR function is relatively understudied, and more work is required to determine whether lobular subtypes behave similarly to their invasive ductal carcinoma counterparts. Importantly, understanding GR signaling in individual breast cancer subtypes has potential clinical implications because of the recent development of highly selective GR non-steroidal ligands, which represent a therapeutic approach for modulating GR activity systemically.

We provide compelling evidence that high CDK2 is a feature of aggressive breast cancers. The clinical evaluation of CDK2 inhibitors in early-stage BC patients will have a clinical impact.

rTNM staging system has an outstanding prognostic value for survival outcome of patients with IBTR, and IBTR and primary EBC may have potentially analogous features in the context of TNM staging. BCS plus radiation therapy may be an alternative. IBTR cases who have experienced recurrence with short intervals and with ER-negative tumors might benefit from chemotherapy.

Patients with HER2-positive BC undergoing NAT develop varying degrees of abnormalities (elevated or decreased) in FBG, FTG, and FTC; moreover, the status of FTG levels during NAT may predict pCR in ER-negative or PR-negative HER2-positive BC.Early monitoring and timely intervention for FTG abnormalities may enable this subset of patients to increase the likelihood of obtaining a pCR along with management of abnormal markers.

The methylation of IL21R showed efficient discriminatory power to distinguish benign breast tumours from BC (area under curve (AUC) = 0.88), and especially from ER-negative BC (AUC = 0.95), PR-negative BC (AUC = 0.93) and triple-negative BC (AUC = 0.96). We disclosed significant IL21R hypomethylation in patients with BC compared to women with benign breast tumours, and revealed the somatic change of DNA methylation could be a potential biomarker for molecular pathology of BC.

Mechanistic analysis revealed a potential role of Resf1 in transcriptional control through association with compound G4 quadruplexes in expressed sequences, particularly those associated with ribosomal biogenesis. These results suggest that loss of Resf1 enhances tumor progression in ER- breast cancer through multiple alterations in both transcriptional and translational control.

P2, N=56, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

P=N/A, N=98, Recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Aug 2023 --> Aug 2024

Our study delineates changes in the treatment and survival of pMBC over two decades. Stage migration, screening introduction, and changes in registration practice, however, prevent a valid assessment of a possible causal relationship.

We observed striking racial and ethnic differences in second cancer risk among breast cancer survivors. Additional research is needed to inform targeted approaches for early detection strategies and treatment to reduce these racial and ethnic disparities.

The association between ER and breast cancer prognosis was most strongly mediated by H4K20me3 (29.07% for OS; 22.42% for PFS), followed by H3K4me2 (11.5% for OS; 10.82% for PFS) and least by H3K9me2 (9.35% for OS; 7.34% for PFS). H4K20me3, H3K4me2 and H3K9me2 mediated the relationship between ER and breast cancer prognosis, which would help to further elucidate the impact of ER on breast cancer prognosis from an epigenetic perspective and provide new ideas for breast cancer treatment.

The distribution of the molecular subclasses in stage IV endometrial cancer patients differed substantially from the distribution in stage I-III endometrial cancer patients, with the unfavorable subclasses being more frequently present. Although the molecular classification was not prognostic in stage IV endometrial cancer, it could guide adjuvant treatment decisions.

Our study revealed that plasma metabolites were significantly different between recurrent and non-recurrent patients, proposing therapeutic insights for breast cancer prognosis.

No such associations were observed for BRCA2 carriers. These results should inform genetic counseling, prevention, and treatment strategies for BRCA PV carriers.

The findings reveal that phosphatidylinositol and triglycerides levels decreased the risk of BC, indicating a potential protective role of these lipid molecules. Moreover, the study elucidates BC's intricate lipid metabolic pathways, highlighting diverse lipidome structural variations that may have varying effects in different molecular subtypes.

In this study, we found that the allele A of the FGFR2-rs13387042 polymorphism is associated with increased risk of developing breast cancer. This study underscores its potential as a genetic marker for personalized risk assessment and targeted interventions.

The data from this study provide multi-institutional benchmark data to assist laboratories performing periodic comparisons as part of a quality management program. Overall expression rates were generally similar to those of other published reports, with the exception of the ER-negative and HER2-positive rates, both of which were somewhat lower.

The results suggest that psoriasis may increase the risk of BC, especially ER- BC, while reverse MR suggests a decreased risk of psoriasis in Her2+ BC. Transcriptome analysis revealed a shared mechanism between psoriasis and BC.

P3, N=382, Not yet recruiting, Biocon Biologics UK Ltd | Initiation date: Mar 2024 --> Sep 2024

P3, N=900, Active, not recruiting, Shanghai Henlius Biotech | Recruiting --> Active, not recruiting

MBC was found to be triple negative in most cases, but a significant percentage were HR (ER/PR) positive. Moreover, we found an association between HR status and various clinicopathological features, indicating that HR status is a significant predictor of MBC prognosis.

HER2-positive breast cancer exhibited three distinct HR-specific subtypes with varying clinical manifestations and treatment responses. These findings suggest personalized treatment strategies considering ER and PR expression patterns, emphasizing the need for further investigations to unravel molecular traits underlying HER2-positive breast cancer with distinct HR expression patterns.

Knockdown of GPR39 partially impeded permethrin-induced cellular proliferation and altered the expression of proliferation marker protein PCNA and cell cycle-associated protein cyclin D1 via the ERK1/2 signaling pathway. These findings offer novel evidence for permethrin as an environmental breast cancer risk factor, displaying its potential to impact breast cancer cell proliferation via an estrogen receptor-independent pathway.

P1, N=22, Completed, Barbara Parker, MD | Active, not recruiting --> Completed | Phase classification: P1b --> P1

P2, N=50, Recruiting, Wake Forest University Health Sciences | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

P3, N=1550, Active, not recruiting, NSABP Foundation Inc | Trial completion date: Jun 2025 --> Nov 2027

P2, N=99, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

In conclusion, this study demonstrates that 4-OH-E1 is a novel inhibitor of PDI and can strongly inhibit ferroptosis in human breast cancer cells in an estrogen receptor-independent manner. The mechanistic understanding gained from the present study may also aid in understanding the estrogen receptor-independent cytoprotective actions of endogenous estrogen metabolites in many noncancer cell types.

EB1089 significantly enhanced the cell growth inhibitory effect of lapatinib combined with antiestrogens in HER2-positive breast cancer cells by modulating ERα expression and Akt phosphorylation suppression. These results highlight the potential of this therapeutic approach as a promising strategy for managing HER2-positive breast cancer.

In our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.

Patients with HER2 normal MBC receiving monotherapy capecitabine had a median PFS of 4.3 months, and a median OS of 14 months. PFS was consistent regardless of treatment line but differed significantly according to ER status.

P1/2, N=75, Recruiting, Massachusetts General Hospital | Phase classification: P1b/2 --> P1/2 | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2025

The BRENDA-Score accurately predicted 5-year and 10-year MFS. The results showed good validity, transportability, and potential clinical value. However, the results for 5-years MFS should be interpreted carefully in patients aged <40 years. After 10 years the value of the ER as a prognostic factor was less important.

Black and younger women with breast cancer have a higher burden of BIRC5-high tumors than older and non-Black women. Emerging anti-survivin treatment strategies may be an important future direction for equitable breast cancer outcomes.

Our study comprehensively examined how differences in common variation contribute to molecular differences between ER + and ER- BC and introduces a novel, splicing-based framework that can be used in future TWAS studies.

This study did not find a significant difference in HPV expression between breast cancer and non-malignant breast tumors; however, the higher percentage of HPV in ER-positive compared to ER-negative breast cancer warrants further attention.

ODX does not appear to add significant additional information to inform treatment decisions for most patients with ER-low BC. Incorporating weak ER staining intensity in addition to low percentage of nuclear positivity identifies about twice as many ER-low patients, although with reduced specificity for high RS. Our study supports the contention that most ER-low early BC should be regarded similarly to ER-negative BC.

The automated ER AI algorithm demonstrated excellent concordance with pathologists' assessments and accurately differentiated ER-positive from ER-negative metastatic breast carcinoma cytology cases. However, precision in identifying tumour cells in cytology specimens requires further enhancement.