CIRCULATING TUMOR DNA OF CEREBROSPINAL FLUID SAMPLES IN TRIPLE-NEGATIVE BREAST CANCER

USEFULNESS OF LONGITUDINAL ASSESSMENT FOR EARLY DETECTION OF BRAIN METASTASIS

Authors

  • Lucrezia Raimondi Sapienza University of Rome
  • Laura Di Benedetto BIOS SpA
  • Paolo Ciracì University of Bordeaux
  • Rachele Lazzeroni Sant’Andrea University Hospital
  • Filippo Maria Raimondi E-Campus University
  • Gian Paolo Spinelli Sapienza University of Rome
  • Giuseppe Naso Policlinico Umberto I

Keywords:

Triple-Negative Breast Cancer, Brain Metastasis, Circulating Tumor DNA, Liquid Biopsy, Predictive Biomarkers

Abstract

Objectives: Triple-negative breast cancer (TNBC) still has poor prognosis for a higher rate of relapse and a greater tendency of developing brain metastasis (BrM) compared with other major breast cancer subtypes. Circulating tumor DNA (ctDNA) represents a valuable tool associated with the outcome and the aggressiveness of breast cancer. Biomarkers allowing to predict the development of BrM in TNBC are needed. We studied the usefulness of assessment of CSF-ctDNA for identification early at-risk patients to develop BrM in TNBC. Methodology: A total of 323 newly diagnosed nonmetastatic TNBC patients who underwent neoadjuvant therapy + surgery (NACT) with complete response (CR) were prospectively enrolled. After surgery, CSF-ctDNA collected from all patients enrolled was extracted and assessed using the QIAamp Circulating Nucleic Acid Kit. Survival curves were estimated by using Kaplan–Meier method and compared with the log-rank test. Multivariate Cox regression was used to identify the risk of mortality at 3 years. Results: After NACT, CSF-ctDNA was detectable in 126/323 (39%) patients, 101/126 (80%) were diagnosed at Stage 3. A total of 124 out of 126 (98.4%) ctDNA+ patients subsequently developed BrM. In contrast, only 2 (2/197, 1%) ctDNA− patients subsequently developed BrM and 195 other patients remain in a CR (p<0.001, Fisher’s exact test). CSF-ctDNA did associate with PFS and OS: undetectable ctDNA was associated with superior PFS (HR 0.3; p=0.002) and OS (HR 0.2; p<0.01), indicating survival is largely determined by the onset of BrM. With a median follow-up of 3 years, median PFS of ctDNA+ versus ctDNA− patients was 13 months versus not reach, p=0.004 (log-rank test). Median OS for ctDNA+ versus ctDNA− patients was 16 months after NACT versus not reach, p=0.0016 (log-rank test). At multivariate analysis, detectable CSF-ctDNA emerged as the best predictor of the development of BrM and 24-month mortality (HR: 3.62; p<0.0001). Age, stage, Ki67%, and response to chemotherapy were not significantly associated with the prognosis. Conclusion: After NACT, detectable CSF-ctDNA significantly associated with PFS and OS, identifying early at-risk patients to develop BrM in TNBC who should take advantage from appropriate additional treatment, remains a critical problem.

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Author Biographies

Lucrezia Raimondi, Sapienza University of Rome

U.O.C. Territorial Oncology of Aprilia, Sapienza University of Rome

Paolo Ciracì, University of Bordeaux

Institut National de la Santé et de la Recherche Médicale (INSERM) U 1053, Research in Translational Oncology, University of Bordeaux

Rachele Lazzeroni, Sant’Andrea University Hospital

Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, Sant’Andrea University Hospital

Filippo Maria Raimondi, E-Campus University

Biostatistical Consultant, E-Campus University

Giuseppe Naso, Policlinico Umberto I

Division of Medical Oncology, Policlinico Umberto I

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Published

2021-10-14

How to Cite

Raimondi, L., Benedetto, L. D., Ciracì, P., Lazzeroni, R., Raimondi, F. M., Spinelli, G. P., & Naso, G. (2021). CIRCULATING TUMOR DNA OF CEREBROSPINAL FLUID SAMPLES IN TRIPLE-NEGATIVE BREAST CANCER: USEFULNESS OF LONGITUDINAL ASSESSMENT FOR EARLY DETECTION OF BRAIN METASTASIS. Mastology, 31, 8. Retrieved from https://revistamastology.emnuvens.com.br/revista/article/view/980

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Section

Oral Presentation