The role of germline genetics in adjuvant aromatase inhibitor (AI) treatment efficacy in ER-positive breast cancer is poorly understood. We employed a two-stage candidate gene approach to examine associations between survival endpoints and common germline variants in 753 endocrine resistance-related genes. For a discovery cohort, we screened the Breast Cancer Association Consortium database (n ≥ 90,000 cases) and retrieved 2789 AI-treated patients. Cox model-based analysis revealed 125 variants associated with overall, distant relapse-free, and relapse-free survival (p-value ≤ 1E-04). In validation analysis using five independent cohorts (n = 8857), none of the six selected candidates representing major linkage blocks at CELA2B/CASP9, NR1I2/GSK3B, LRP1B, and MIR143HG (CARMN) were validated. We discuss potential reasons for the failed validation and replication of published findings, including study/treatment heterogeneity and other limitations inherent to genomic treatment outcome studies. For the future, we envision prospective longitudinal studies with sufficiently long follow-up and endpoints that reflect the dynamic nature of endocrine resistance.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840073 | PMC |
| http://dx.doi.org/10.1038/s41523-025-00733-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
European cancer mortality predictions for the year 2025 with focus on breast cancer.
Ann Oncol
February 2025
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. Electronic address:
Background: We predicted the number of cancer deaths and rates for 2025 in the European Union (EU), its five most populous countries, and the UK, focusing on breast cancer.
Materials And Methods: We derived population data and death certificates for all cancers and major sites for the EU, France, Germany, Italy, Poland, Spain, and the UK since 1970, from the World Health Organization and United Nations databases. Estimates for 2025 were computed by linear regression on recent trends identified through Poisson joinpoint regression, considering the slope of the most recent trend segment.
Response to "The Impact of Baseline Comorbidities and Performance Status on HER2-Targeted Therapy Outcomes".
Clin Breast Cancer
February 2025
Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute for Breast Cancer Precision Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:
Comparative Assessment of Real-Time and Offline Short-Lag Spatial Coherence Imaging of Ultrasound Breast Masses.
Ultrasound Med Biol
March 2025
Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA; Department of Electrical & Computer Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA. Electronic address:
Objective: To perform the first known investigation of differences between real-time and offline B-mode and short-lag spatial coherence (SLSC) images when evaluating fluid or solid content in 60 hypoechoic breast masses.
Methods: Real-time and retrospective (i.e.
Cell-free supernatant of Clostridium leptum inhibits breast cancer cell proliferation.
Lett Appl Microbiol
March 2025
Zhejiang Provincial International S&T Cooperation Base for Active Ingredients of Medicinal and Edible Plants and Health, Zhejiang Provincial Key TCM Laboratory for Chinese Resource Innovation and Transformation, School of Pharmaceutical Sciences, Jinhua Academy, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Breast cancer has emerged as the leading cause of global cancer incidence, surpassing lung cancer. Accumulating evidence suggests that probiotics exhibit inhibitory effect on breast cancer progression, highlighting the need to identify gut flora-derived probiotics with potential anti-breast cancer properties. Here, we investigated the effect of the cell-free supernatant of C.
View Article and Find Full Text PDFA comparative study on antioxidant properties, total phenolics, total flavonoid contents, and cytotoxic properties of marine green microalgae and diatoms.
J Genet Eng Biotechnol
March 2025
Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Aquatic Animal Health and Therapeutics Laboratory (AquaHealth), Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Bioprocessing and Biomanufacturing Research Complex, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. Electronic address:
Despite having valuable and novel metabolites, the marine microalgae species are still not thoroughly investigated for their pharmaceutical and nutraceutical importance. Therefore, this study was focused on investigating the crude extracts of marine green microalgae species, Tetraselmis sp., Nannochloropsis sp.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!