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<p>In this large, real-world, translational research cohort of 708 patients in the Tempus database who had hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2−) metastatic breast cancer with prior cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) exposure, low-level Aurora kinase A (<i>AURKA</i>) copy-number (CN) gain was common, occurring in 106/708 patients (15.0%). These low-amplification (LA) events impacted RNA expression: patient samples with wild-type <i>AURKA</i> CN had significantly lower median <i>AURKA</i> RNA expression levels than did those with LA or amplified <i>AURKA</i>. Further, LA <i>AURKA</i> CN predicted inferior outcomes on CDK4/6i for patients with HR+, HER2− metastatic breast cancer: real-world progression-free survival was 16.9 months for wild type and 9.3 months for LA <i>AURKA</i> CN (hazard ratio, 1.74; 95% confidence interval, 1.42–2.13; <i>P</i> = 0.0003). These novel results represent the first real-world validation of LA <i>AURKA</i> CN gain as a potential predictor of CDK4/6i resistance.</p>

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Low-level Aurora kinase A amplification: CDK4/6 inhibitor resistance biomarker in hormone receptor-positive metastatic breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月29日

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  • Seth A. Wander,
  • Lisa D. Eli,
  • Ezgi Karaesmen Rizvi,
  • Roosheel Sandeep Patel,
  • Emily Schultz,
  • Agnieszka K. Witkiewicz,
  • Georg F. Bischof,
  • Erik S. Knudsen,
  • Karthik V. Giridhar

摘要

In this large, real-world, translational research cohort of 708 patients in the Tempus database who had hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2−) metastatic breast cancer with prior cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) exposure, low-level Aurora kinase A (AURKA) copy-number (CN) gain was common, occurring in 106/708 patients (15.0%). These low-amplification (LA) events impacted RNA expression: patient samples with wild-type AURKA CN had significantly lower median AURKA RNA expression levels than did those with LA or amplified AURKA. Further, LA AURKA CN predicted inferior outcomes on CDK4/6i for patients with HR+, HER2− metastatic breast cancer: real-world progression-free survival was 16.9 months for wild type and 9.3 months for LA AURKA CN (hazard ratio, 1.74; 95% confidence interval, 1.42–2.13; P = 0.0003). These novel results represent the first real-world validation of LA AURKA CN gain as a potential predictor of CDK4/6i resistance.