Association of post-operative ctDNA detection with outcomes of patients with early breast cancers.

Autor:	Cutts R; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London., Ulrich L; Breast Unit, Royal Marsden Hospital, London, UK., Beaney M; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London., Robert M; Department of Breast Medical Oncology and Neuro-Oncology, Early Therapeutic Unit, Institute of Oncology de l'Ouest, St Herblain, France., Coakley M; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London., Bunce C; Clinical Trials Unit, Royal Marsden Hospital, London, UK., Crestani GW; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London., Hrebien S; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London., Kalashnikova E; Natera, Inc., Austin, USA., Wu HT; Natera, Inc., Austin, USA., Dashner S; Natera, Inc., Austin, USA., Sethi H; Natera, Inc., Austin, USA., Aleshin A; Natera, Inc., Austin, USA., Liu M; Natera, Inc., Austin, USA., Ring A; Breast Unit, Royal Marsden Hospital, London, UK., Okines A; Breast Unit, Royal Marsden Hospital, London, UK., Smith IE; Breast Unit, Royal Marsden Hospital, London, UK., Barry P; Breast Unit, Royal Marsden Hospital, London, UK., Turner NC; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London; Breast Unit, Royal Marsden Hospital, London, UK; The Ralph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital, London, UK., Garcia-Murillas I; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London. Electronic address: isaac.garcia-murillas@icr.ac.uk.
Jazyk:	angličtina
Zdroj:	ESMO open [ESMO Open] 2024 Sep; Vol. 9 (9), pp. 103687. Date of Electronic Publication: 2024 Aug 30.
DOI:	10.1016/j.esmoop.2024.103687
Abstrakt:	Background: In early breast cancer (EBC) patients, we aimed to determine whether circulating tumor DNA (ctDNA) analysis following primary surgery, before systemic therapy, identified molecular residual disease and was associated with risk of relapse and relapse-free survival (RFS). Methods: Plasma was collected, retrospectively, before surgery, 1-14 weeks post-operatively, and before adjuvant therapy, and in a subset of patients after adjuvant therapy. A personalized, tumor-informed, multiplex PCR next generation sequencing assay (Signatera™) was used for ctDNA detection and quantification. The primary objective was to compare RFS and distant recurrence-free survival (DRFS) in patients with detected versus non-detected ctDNA. Results: A total of 48 patients with EBC (median age 50.5 years) [34 hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), 5 HER2+, 9 triple-negative breast cancer) were included. ctDNA was detected in 64.5% (20/31) of patients before surgery, and 35.4% (17/48) after surgery. ctDNA detection before surgery was associated with tumor grade (P = 0.019), ctDNA detection after surgery was associated with receptor subtype (P = 0.01). Patients with ctDNA detected after surgery had worse DRFS [hazard ratio = 5.5, 95% confidence interval (CI) 1.1-28.5, P = 0.04]. RFS in patients with ctDNA detected after surgery was worse than in those with lack of ctDNA detection, although not statistically significant (hazard ratio = 3.7, 95% CI 0.9-15.7, P = 0.073). Patients with ctDNA detected preoperatively or post-operatively had a trend towards worse RFS (hazard ratio = 7.8, 95% CI 0.9-63.7, P = 0.05) and DRFS (hazard ratio = 6.8, 95% CI 0.8-57, P = 0.07) compared with those with ctDNA undetected at both timepoints. ctDNA detection anticipated clinical relapse with a median lead time of 16 months. Conclusions: In patients with treatment-naive EBC, ctDNA is detectable after surgery. The absence of ctDNA at a single post-surgical timepoint is associated with improved DRFS, supporting the development of future trials studying de-escalation of systemic therapy. (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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