Blood-based genomics of triple-negative breast cancer progression in patients treated with neoadjuvant chemotherapy

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V. Appierto¹  M. Silvestri¹  R. Miceli²  S. Veneroni¹  S. Folli³  G. Pruneri⁴  A. Vingiani⁴  A. Belfiore⁴  V. Cappelletti¹  M. Vismara¹  F. Dell¹  L. De Cecco⁵  G.V. Bianchi⁶  F.G. de Braud⁶  M.G. Daidone¹  S. Di Cosimo¹  E. Ortolan¹ 

[1] Biomarkers Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori;Clinical Epidemiology and Trial Organization Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori;Breast Cancer Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori;Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori;Integrated Biology Platform, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori;Department of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori

关键词: circulating tumor DNA;    circulating tumor cells;    neoadjuvant chemotherapy;    triple-negative breast cancer;    prognosis;   

DOI  :  10.1016/j.esmoop.2021.100086

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background As neoadjuvant chemotherapy (NAC) is increasingly used in triple-negative breast cancer (TNBC), we investigated the value of circulating tumor DNA (ctDNA) for patient monitoring prior, during, and after NAC, and circulating tumor cells (CTCs) for disease characterization at clinical progression.Materials and methods Forty-two TNBC patients undergoing NAC were prospectively enrolled. Primary tumor mutations identified by targeted-gene sequencing were validated and tracked in 168 plasma samples longitudinally collected at multiple time-points by droplet digital polymerase chain reaction. At progression, plasma DNA underwent direct targeted-gene assay, and CTCs were collected and analyzed for copy number alterations (CNAs) by low-pass whole genome sequencing.Results ctDNA detection after NAC was associated with increased risk of relapse, with 2-year event-free survival estimates being 44.4% [95% confidence interval (CI) 21.4%-92.3%] versus 77.4% (95% CI 57.8%-100%). ctDNA prognostic value remained worthy even after adjusting for age, residual disease, systemic inflammatory indices, and Ki-67 [hazard ratio (HR) 1.91; 95% CI 0.51-7.08]. During follow-up, ctDNA was undetectable in non-recurrent cases with the unique exception of one showing a temporary peak over eight samples. Conversely, ctDNA was detected in 8/11 recurrent cases, and predated the clinical diagnosis up to 13 months. Notably, recurrent cases without ctDNA developed locoregional, contralateral, and bone-only disease. At clinical progression, CTCs presented chromosome 10 and 21q CNAs whose network analysis showed connected modules including HER/PI3K/Ras/JAK signaling and immune response.Conclusion ctDNA is not only associated with but is also predictive of prognosis in TNBC patients receiving NAC, and represents an exploitable tool, either alone or with CTCs, for personalized TNBC management.

【 授权许可】

CC BY|CC BY-NC-ND