ESR1

This study performed whole genome and transcriptome sequencing on 50 tumor samples from 37 patients with locally advanced or metastatic breast cancer. It uncovered extensive genomic complexity, with triple-negative breast cancer (TNBC) showing the highest tumor mutational burden. Homologous recombination deficiency (HRD) was found in 27% of patients, frequently in BRCA1/2 wild-type cases due to deleterious structural variants in other repair genes. Therapeutically actionable alterations were identified in 84% of patients, including a novel ESR1::EP300 fusion potentially linked to endocrine resistance. These findings underscore the utility of whole-genome sequencing for characterizing metastatic disease and guiding therapies.

This review examines established and emerging biomarkers for stratifying patients with early-stage breast cancer to optimize adjuvant systemic therapy. It highlights that while clinicopathological factors remain fundamental, decision-making is increasingly driven by precise biological markers. ER and HER2 status are crucial, and multigene assays refine recurrence risk and chemotherapy benefit in hormone receptor-positive cancers. Immune and DNA-repair biomarkers inform targeted therapies in HER2-positive and triple-negative subtypes, while mutation profiling of genes like ESR1, PIK3CA, AKT, MTOR, and PTEN guides targeted treatments. Emerging approaches, including liquid biopsy and artificial intelligence, offer dynamic insights but require prospective validation.

The FIGO staging system for endometrial cancer underwent a significant revision in 2023, incorporating refined anatomical criteria and molecular determinants. This update aims to optimize adjuvant treatment selection by maximizing therapeutic benefits while minimizing harm. Molecular subgroups include POLEmut, p53abn, MMRd, and NSMP. The 2025 ESGO-ESTRO-ESP recommendations further enhance this framework by mandating estrogen receptor (ER) assessment within the NSMP category, identifying early-stage disease with an increased risk of recurrence and mortality.

Data from the 2025 San Antonio Breast Cancer Symposium highlight the expanding role of circulating tumor DNA (ctDNA) in breast cancer management. ctDNA is now being utilized to guide therapeutic decisions, particularly in advanced hormone receptor-positive breast cancer. The SERENA-6 trial demonstrated that ctDNA-detected ESR1 mutations enabled adaptation of endocrine therapy, leading to improved clinical outcomes. Furthermore, in early-stage disease, ctDNA identifies minimal residual disease (MRD) and patients at high risk of recurrence. These advancements position ctDNA as a crucial biomarker for precision oncology and dynamic treatment adaptation.

This meta-analysis investigated the efficacy of rechallenging with CDK4/6 inhibitors (CDK4/6i) after progression in patients with HR-positive, HER2-negative advanced/metastatic breast cancer. The study included 1396 patients from eight clinical trials, comparing CDK4/6i rechallenge plus endocrine therapy to endocrine therapy alone. Results indicated a significant improvement in median progression-free survival (PFS) of 5.8 months versus 3.7 months. A greater benefit was observed when switching to a different CDK4/6 inhibitor, particularly with abemaciclib, but no overall survival benefit was demonstrated.