ER (Estrogen receptor)

Based on preclinical studies showing synergism with simultaneous inhibition of the estrogen receptor (ER), CDK4/6 and PI3K pathways and based on window of opportunity studies showing that metformin suppresses PI3K/mTOR signaling in endometrial cancer (EC), we conduct a non-randomized phase 2 study of letrozole/abemaciclib/metformin in ER positive endometrioid EC (NCT03675893). There are no objective responses among TP53 mutated ECs and among NSMP (no specific molecular profile) tumors with RB1 or CCNE1 alterations; CTNNB1 mutations correlate with clinical benefit. Pharmacokinetic analyses demonstrate that administration of letrozole and abemaciclib with metformin result in a more than 3-fold increase in metformin exposure.

In September 2025, imlunestrant was approved for the treatment of adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy in the USA. This article summarizes the milestones in the development of imlunestrant leading to this first approval for use in patients with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer.

Understanding the mechanisms underlying BRCA1-mediated lineage plasticity offers novel therapeutic avenues to target early-stage tumor initiation and progression in BRCA1-mutated breast cancer. This review perspective sheds light on the role of BRCA1 in lineage plasticity and highlights probable mechanisms by which BRCA1 could promote this lineage plasticity.

Despite these advancements, challenges persist in data heterogeneity and mechanistic interpretation of radiomic biomarkers. Emerging strategies integrating radiogenomic analyses and organoid validation platforms are establishing new paradigms for precision imaging-guided therapy.

TNBC is highly prevalent among Sudanese women, especially those younger than 50 years and those with MC. These findings underscore the importance of early diagnosis and wider access to molecular profiling to guide treatment in low-resource settings.

We previously showed that PR mediates expansion of cancer stem-like cell (CSC) populations and promotes tamoxifen resistance in nuclear ER/PR transcriptional complexes...The UPR activator ErSO, but not UPR inhibitors, blocked expansion of CSCs in WT as well as Y537S ER + models. Together, our findings demonstrate a critical interplay between PR and mutant ER function and provide insight into PR-driven pathways including hyperactivation of the stress-sensing UPR that can be exploited as potential therapeutic avenues in advanced ER+ breast cancer.

We identified unique periods of susceptibility to NO2 and PM2.5 for breast cancer risk by ER status.

ERpHER2n-Basal breast cancer represents a clinically high-risk subgroup whose molecular resemblance to TNBC highlights potential therapeutic opportunities, particularly for immunotherapy and DNA repair-targeting treatments.

Our study suggests that postoperative RT is associated with improved survival in most DCIS patients. The nomograms showed good performance in predicting the DSS and DFS of DCIS patients, and our online tool well visualized the DSS and DFS prediction to support clinical decision-making.

Differential expression analysis and co-expression network construction revealed 154 candidate TEX-related genes, from which five prognostically significant genes were selected to construct a risk scoring model.ResultsOur findings indicate that TEX characteristics are crucial for prognostic assessment in TNBC patients, with significant correlations between risk scores and tumor-infiltrating immune cells. High-risk patients exhibited elevated expression levels of immune checkpoint genes, suggesting potential implications for immunotherapy.ConclusionsThis study underscores the clinical significance of TEX features in TNBC prognosis and highlights the urgent need for therapeutic strategies targeting TEX to improve patient outcomes.

In conclusion, the present investigation reveals a noteworthy correlation between elevated levels of MRP2 protein in CTCs and TNBC. This finding deepens our understanding of the molecular mechanisms that contribute to the metastasis of breast cancer and provides a scientific basis for predicting treatment outcomes in breast cancer patients exhibiting elevated levels of MRP2 protein expression.

Functional assays in both T47D and MCF7 cells demonstrated that co-expression of N4BP2L2 restored HR activity and reduced olaparib sensitivity in EXO1-overexpressing cells. These findings suggest EXO1 overexpression serves as a marker of functional HR deficiency and a potential predictor of PARP inhibitor response, highlighting the EXO1-N4BP2L2 axis as a promising biomarker and therapeutic target, especially for guiding PARP inhibitor use beyond BRCA-mutated tumors.