Establishment of Risk Prediction Model for Brain Metastasis with Breast Cancer by Using ctDNA Genetic Profile and Clinical Features from Real-World Data

Abstract

Background: The survival status of patients with breast cancer with brain metastases (BCBM) is not optimistic, thus understanding of the patient clinical and genetic aberrations is critical for offering appropriate treatment regimens and forecasting the prognoses of the BCBM patients. Methods: The trial was designed as a real-world study. 146 BCBM patients were recruited and their clinical features were analyzed for evaluating overall survival (OS). For genetic testing, 30 BCBM and 165 non-BM BC patients from Hunan Cancer Hospital, and 86 BCBM and 1416 non-BM BC patients from Geneplus database received ctDNA testing was compared and analyzed. Results: For 146 BCBM patients, Ki67 >14% and >3 metastatic brain tumors were significant risk factors associated with poor overall survival (OS), while chemotherapy and brain radiotherapy were beneficial factors for better OS. Compared to non-BM metastatic breast cancer (MBC) patients, BCBM patients had significantly more fibroblast growth factor receptor (FGFR) genetic aberrations. The combination of FGFR, TP53 and FLT1 genetic aberrations plus immunohistochemisty (IHC) HER2-positive could effectively predict brain metastases (AUC=77.13%). FGFR aberration alone was not only a prediction factor (AUC=67.90%), but also a significant risk factor for poor PFS in MBC patients (Logrank p=0.029). Among FGFR family members, FGFR1 was the most frequent aberration and significantly higher in BMBC patients. When further evaluating the genetic response of anti-cancer treatment by ctDNA testing, the frequency of FGFR genetic aberrations could be suppressed by capecitabine-based treatment. Conclusion: A group of clinical and genetic events could forecast the occurrence of brain metastases in breast cancers, including FGFR, TP53 and FLT1 genetic aberrations, and IHC HER2-positive. Moreover, FGFR genetic aberration alone could predict poor prognosis. Funding Statement: Development and Reform Commission of Hunan Province (CN) Hunan Key Research Project No. 2018SK2124 (Recipient: Quchang Ouyang); Hunan Provincial Health and Sanitation Committee Project No. 2019070 (Recipient: Zhe-Yu Hu); Hunan Provincial Natural Science Youth Foundation Project No.20190988 (Recipient: Zhe-Yu Hu). Declaration of Interests: The authors declare that they have no conflict of interests. Ethics Approval Statement: The study was approved by the Ethics Committee at Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine/Central South University.