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Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases
  1. Giulia Siravegna1,
  2. Elena Geuna2,
  3. Benedetta Mussolin1,
  4. Giovanni Crisafulli1,3,
  5. Alice Bartolini1,
  6. Danilo Galizia2,
  7. Laura Casorzo1,
  8. Ivana Sarotto1,
  9. Maurizio Scaltriti4,5,
  10. Anna Sapino1,6,
  11. Alberto Bardelli1,3,
  12. Filippo Montemurro2
  1. 1 Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy
  2. 2 Investigative Clinical Oncology (INCO), Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy
  3. 3 Department of Oncology, University of Torino, Candiolo, Italy
  4. 4 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New Jersey, USA
  5. 5 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
  6. 6 Department of Medical Sciences, University of Torino, Torino, Italy
  1. Correspondence to Professor Alberto Bardelli; alberto.bardelli{at}


Background Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution.

Methods In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment.

Results Baseline CSF-derived ctDNA analysis revealed TP53 and PIK3CA mutations as well as ERBB2 and cMYC amplification. Post-treatment ctDNA analysis showed decreased markers level in plasma, consistent with extra-CNS disease control, while increased in the CSF, confirming poor treatment benefit in the CNS.

Discussion Analysis of ctDNA in the CSF of HER2-positive mBC is feasible and could represent a useful companion for clinical management of brain metastases.

  • liquid biopsy
  • breast cancer
  • cerebrospinal fluid
  • HER2 positive
  • heterogeneity

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  • GS and EG are co-first authors. AB and FM are co-senior authors.

  • Handling editor Christoph C Zielinski

  • Contributors GS, A Bardelli, EG and FM designed the study and wrote the manuscript. GS, BM, A Bartolini, GC, LC and IS performed the experiments and acquired the data. A Bardelli, AS and FM supervised the study. All authors revised and approved the manuscript.

  • Competing interests FM has received speakers Honoraria from Novartis, Astra Zeneca and Roche and travel grants from Astra Zeneca and Roche. All other authors declare no conflicts of interests.

  • Patient consent Obtained.

  • Ethics approval Ethical Committee of Candiolo Cancer Institute.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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