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August 16, 2025npj Breast CancerOpen Access

Circulating genomic landscape following cyclin-dependent kinase 4/6 inhibitors exposure in HR + /HER2− metastatic breast cancer: a retrospective multi-institutional Consortium analysis

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Authors

LPLetizia PontolilloADAndrew A. DavisLGLorenzo Gerratana

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Overview

Retrospective analysis reveals specific gene alterations in HR+/HER2- metastatic breast cancer, suggesting CDK4/6i resistance mechanisms and prognostic factors.

Key Points

  • CDK4/6 inhibitors treatment led to significant gene alterations, impacting patient outcomes.
  • ESR1 mutations were found in 46.2% of patients, highlighting a key resistance mechanism against therapy.
  • Next-generation sequencing was utilized to analyze circulating tumor DNA in a cohort of 93 patients.
  • Low-mutant allele frequency correlates with improved progression-free and overall survival rates.

Cite This Study

Pontolillo et al. (2025) studied this question.

synapsesocial.com/papers/68af2d7ccf1dd9ea359e592chttps://doi.org/10.1038/s41523-025-00802-2
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Cyclin-dependent kinase 4/6 inhibitors beyond progression in hormone receptor-positive, HER2-negative advanced breast cancer: a systematic review and meta-analysis (REIGNITE study)2025
  2. 2Real-World Predictors of Survival in CDK4/6 Inhibitor-Treated Metastatic Breast Cancer: The Significance of ER Expression Level and Treatment Naivety2025
  3. 3Comparative long-term outcomes of first-line CDK4/6 inhibitors plus endocrine therapy versus endocrine therapy in patients with HR+/HER2-metastatic or advanced breast cancer: a meta-analysis2025 · 4 citations
  4. 4Treatment consequence and adverse events of cyclin-dependent kinase 4/6 inhibitors on patients with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and meta-analysis2025
  5. 5Clinical significance on switching CDK4/6 inhibitors among 13,284 patients with metastatic breast cancer2025