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<p>Breast cancer (BC) is a leading cause of cancer-related morbidity and mortality in women, with many patients developing brain metastases (BM). Stereotactic radiosurgery (SRS) has become a standard treatment for BCBM, achieving local control rates exceeding 90%. However, some patients remain resistant to SRS, and genetic factors may influence treatment outcomes. We aimed to evaluate the impact of <i>CHEK2</i> mutations on radiation response and local control in patients with BCBM treated with SRS. We analyzed 11 patients with confirmed pathogenic <i>CHEK2</i> mutations and 43 total BCBM treated with CyberKnife SRS. Data on demographics, performance status, and tumor characteristics were collected. Primary endpoints included local control and distant BM-free survival, while secondary endpoints were the rate of post-SRS leptomeningeal disease (LMD) and the need for additional intervention. The female-to-male ratio was 10:1, with a median age at BC diagnosis of 52 years (range 35-76). Receptor status showed 7 patients were HR<sup>+</sup>/HER2<sup>-</sup>, 2 patients were HR<sup>+</sup>/HER2<sup>+</sup>, 1 patient was HR<sup>-</sup>/HER2<sup>+</sup>, and 1 patient had triple-negative breast cancer. There was a median of 3 BCBM (range 1-6) at presentation, with 7 patients also having extracranial metastasis. Median age at SRS was 55 years (range 41-86), and all patients received systemic chemotherapy prior to SRS. Median maximum diameter of BCBM was 9.0 mm (range 2.6-32.0), with a median prescribed dose of 22 Gy (range 20-30). Median radiographic follow-up was 18.7 months (range 1.9-107.8). Local control rates were 97.8%, 90.9%, and 72.7% at 3, 6, and, 12 months, respectively. Four patients developed LMD and 4 experienced distant recurrence, requiring additional treatment. Local control and distant recurrence rates in patients with <i>CHEK2</i> mutations were notably unfavorable compared to prior reports of SRS outcomes for BCBM. This suggests <i>CHEK2</i> as a potential marker of poor prognosis in BCBM, although direct comparisons to <i>CHEK2</i>-wildtype patients are needed.</p>

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The impact of CHEK2 status on radiosurgical outcomes in breast cancer brain metastases

  • 期刊论文

  • 发表日期：

    2026年4月11日

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  • Paul M. Harary,
  • Yusuke S. Hori,
  • Ahed H. Kattaa,
  • Sze Kiat Tan,
  • Fred C. Lam,
  • Neeraj Kalra,
  • Nirmeen Zagzoog,
  • Armine Tayag,
  • Louisa Ustrzynski,
  • Sara C. Emrich,
  • Iris C. Gibbs,
  • Gordon Li,
  • Atsushi Kuno,
  • David J. Park,
  • Steven D. Chang

摘要

Breast cancer (BC) is a leading cause of cancer-related morbidity and mortality in women, with many patients developing brain metastases (BM). Stereotactic radiosurgery (SRS) has become a standard treatment for BCBM, achieving local control rates exceeding 90%. However, some patients remain resistant to SRS, and genetic factors may influence treatment outcomes. We aimed to evaluate the impact of CHEK2 mutations on radiation response and local control in patients with BCBM treated with SRS. We analyzed 11 patients with confirmed pathogenic CHEK2 mutations and 43 total BCBM treated with CyberKnife SRS. Data on demographics, performance status, and tumor characteristics were collected. Primary endpoints included local control and distant BM-free survival, while secondary endpoints were the rate of post-SRS leptomeningeal disease (LMD) and the need for additional intervention. The female-to-male ratio was 10:1, with a median age at BC diagnosis of 52 years (range 35-76). Receptor status showed 7 patients were HR+/HER2-, 2 patients were HR+/HER2+, 1 patient was HR-/HER2+, and 1 patient had triple-negative breast cancer. There was a median of 3 BCBM (range 1-6) at presentation, with 7 patients also having extracranial metastasis. Median age at SRS was 55 years (range 41-86), and all patients received systemic chemotherapy prior to SRS. Median maximum diameter of BCBM was 9.0 mm (range 2.6-32.0), with a median prescribed dose of 22 Gy (range 20-30). Median radiographic follow-up was 18.7 months (range 1.9-107.8). Local control rates were 97.8%, 90.9%, and 72.7% at 3, 6, and, 12 months, respectively. Four patients developed LMD and 4 experienced distant recurrence, requiring additional treatment. Local control and distant recurrence rates in patients with CHEK2 mutations were notably unfavorable compared to prior reports of SRS outcomes for BCBM. This suggests CHEK2 as a potential marker of poor prognosis in BCBM, although direct comparisons to CHEK2-wildtype patients are needed.