FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients

Ning Xie, Can Tian, Hui Wu, Xiaohong Yang, Liping liu, Jing Li, Huawu Xiao, Jianxiang Gao, Jun Lu, Xuming Hu, Min Cao, Zhengrong Shui, Yu Tang, Xiao Wang, Jianbo Yang, Zhe Yu Hu, Quchang Ouyang

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3 Scopus citations

Abstract

Background: The survival status of patients with breast cancer and brain metastasis (BCBM) receiving current treatments is poor. Method: We designed a real-world study to investigate using patients’ clinical and genetic aberrations to forecast the prognoses of BCBM patients. We recruited 146 BCBM patients and analyzed their clinical features to evaluate the overall survival (OS). For genetic testing, 30 BCBM and 165 non-brain-metastatic (BM) metastatic breast cancer (MBC) patients from Hunan Cancer Hospital, and 86 BCBM and 1416 non-BM MBC patients from the Geneplus database who received circulating tumor DNA testing, were compared and analyzed. Results: Ki67 >14% and >3 metastatic brain tumors were significant risk factors associated with poor OS, while chemotherapy and brain radiotherapy were beneficial factors for better OS. Compared with non-BM MBC patients, BCBM patients had more fibroblast growth factor receptor (FGFR) aberrations. The combination of FGFR, TP53 and FLT1 aberrations plus immunohistochemistry HER2-positive were associated with an increased risk of brain metastasis (AUC = 77.13%). FGFR aberration alone was not only a predictive factor (AUC = 67.90%), but also a significant risk factor for poor progression-free survival (Logrank p = 0.029). FGFR1 aberration was more frequent than other FGFR family genes in BCBM patients, and FGFR1 aberration was significantly higher in BCBM patients than non-BM MBC patients. Most FGFR1-amplified MBC patients progressed within 3 months of the late-line (>2 lines) treatment. Conclusion: A group of genetic events, including FGFR, TP53 and FLT1 genetic aberrations, and HER2-positivity, forecasted the occurrence of BM in breast cancers. FGFR genetic aberration alone predicted poor prognosis.

Original languageEnglish (US)
JournalTherapeutic Advances in Medical Oncology
Volume12
DOIs
StatePublished - 2020

Bibliographical note

Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Hunan Provincial Natural Science Youth Foundation Project Grant No.2019JJ50356 (Recipient: Zhe-Yu Hu); Hunan Provincial Health and Sanitation Committee Project Grant No. C2019070 (Recipient: Zhe-Yu Hu); Key Research Program in Hunan Social Development Grant No. 2019SK2032 (Recipient: Zhe-Yu Hu); Changsha Science and Technology Project Program No.30749 (Recipient: Zhe-Yu Hu).

Keywords

  • FGFR aberrations
  • HER2-positive
  • PFS and OS
  • breast cancer with brain metastasis
  • circulating tumor DNA

PubMed: MeSH publication types

  • Journal Article

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