Serial CTC/cfDNA assessment for the identification of pathogenic mutations in patients with breast cancer

• Published in: Journal of clinical oncology Vol. 35; no. 15_suppl; p. e23070
• Main Authors: Irie, Hanna, Schmidt, Paul H., Port, Elisa R., Kinoshita, Yayoi, de la Iglesia, Janis, Pisapati, Kereeti, Couri, Ronald, Kolodka, Olivia, Arib, Hanane, Sebra, Robert P., Donovan, Michael Joseph
• Format: Journal Article
• Language: English
• Published: 20.05.2017
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2017.35.15_suppl.e23070

Abstract only e23070 Background: Serial liquid biopsy assessment provides a unique platform for detecting existing and / or emergent resistance mutations; it may be particularly beneficial when patients begin to progress on otherwise effective therapy. We aimed to determine the utility of such an approach for detection of tumor genetic alterations at multiple points during the clinical course of patients diagnosed with breast cancer. Methods: Twenty patients diagnosed with stage I-IV breast cancer (50% with triple negative disease) receiving treatment at the Dubin Center of Mount Sinai were consented for serial CTC/cfDNA collections between October 2015 and November 2016. Circulating tumor cell (CTC)/cell-free DNA (cfDNA) were isolated using Cynvenio’s Liquid Biopsy platform and sequenced utilizing the Hotspot/Oncomine panels. DNA from corresponding patient tumors, when available, was also sequenced. Results: 25% of patients had at least one known pathogenic mutation detected in either cfDNA or CTC DNA in at least one collection; all patients had stage IV disease at collection. Pathogenic mutations detected were in p53 (15%), PIK3CA (10%) and Smad4 (5%). For those patients with available tumor tissue, the same pathogenic mutation was detected in the primary tumor. Mutations were more often detected in cfDNA rather than CTC DNA. Finally, known pathogenic mutations were more consistently detected in serial collections with clinical disease progression and resistance to treatment. Conclusions: Pathogenic mutations were identified in 25% of patients, more frequently in cfDNA and not in every collected sample, supporting serial collection studies to monitor response. Presence of same pathogenic mutations in the patient’s primary tumor suggest a role for surveillance in early stage, as well as advanced disease.