Circulating tumor DNA association with residual cancer burden after neoadjuvant chemotherapy in triple-negative breast cancer in TBCRC 030.

Autor:	Parsons HA; Medical Oncology, Dana-Farber Cancer Institute, Boston; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston; Harvard Medical School, Boston. Electronic address: Heather_Parsons@dfci.harvard.edu., Blewett T; Broad Institute of MIT and Harvard, Cambridge., Chu X; Data Science, Dana-Farber Cancer Institute, Boston., Sridhar S; Broad Institute of MIT and Harvard, Cambridge., Santos K; Medical Oncology, Dana-Farber Cancer Institute, Boston., Xiong K; Broad Institute of MIT and Harvard, Cambridge., Abramson VG; Vanderbilt-Ingram Cancer Center, Nashville., Patel A; Medical Oncology, Dana-Farber Cancer Institute, Boston., Cheng J; Broad Institute of MIT and Harvard, Cambridge., Brufsky A; University of Pittsburgh School of Medicine, Pittsburgh., Rhoades J; Broad Institute of MIT and Harvard, Cambridge., Force J; Duke Cancer Center, Durham., Liu R; Broad Institute of MIT and Harvard, Cambridge., Traina TA; Memorial Sloan Kettering Cancer Center, New York., Carey LA; The University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill., Rimawi MF; Baylor College of Medicine Dan L. Duncan Comprehensive Cancer Center, Houston., Miller KD; Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis., Stearns V; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore., Specht J; Seattle Cancer Care Alliance, Seattle., Falkson C; The University of Alabama at Birmingham, Birmingham., Burstein HJ; Medical Oncology, Dana-Farber Cancer Institute, Boston; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston; Harvard Medical School, Boston., Wolff AC; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore., Winer EP; Medical Oncology, Dana-Farber Cancer Institute, Boston; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston; Harvard Medical School, Boston., Tayob N; Data Science, Dana-Farber Cancer Institute, Boston., Krop IE; Medical Oncology, Dana-Farber Cancer Institute, Boston; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston; Harvard Medical School, Boston., Makrigiorgos GM; Radiation Oncology, Dana-Farber Cancer Institute, Boston, USA., Golub TR; Broad Institute of MIT and Harvard, Cambridge., Mayer EL; Medical Oncology, Dana-Farber Cancer Institute, Boston; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston; Harvard Medical School, Boston. Electronic address: Erica_Mayer@dfci.harvard.edu., Adalsteinsson VA; Broad Institute of MIT and Harvard, Cambridge. Electronic address: viktor@broadinstitute.org.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2023 Oct; Vol. 34 (10), pp. 899-906. Date of Electronic Publication: 2023 Aug 18.
DOI:	10.1016/j.annonc.2023.08.004
Abstrakt:	Background: We aimed to examine circulating tumor DNA (ctDNA) and its association with residual cancer burden (RCB) using an ultrasensitive assay in patients with triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy. Patients and Methods: We identified responders (RCB 0/1) and matched non-responders (RCB 2/3) from the phase II TBCRC 030 prospective study of neoadjuvant paclitaxel versus cisplatin in TNBC. We collected plasma samples at baseline, 3 weeks and 12 weeks (end of therapy). We created personalized ctDNA assays utilizing MAESTRO mutation enrichment sequencing. We explored associations between ctDNA and RCB status and disease recurrence. Results: Of 139 patients, 68 had complete samples and no additional neoadjuvant chemotherapy. Twenty-two were responders and 19 of those had sufficient tissue for whole-genome sequencing. We identified an additional 19 non-responders for a matched case-control analysis of 38 patients using a MAESTRO ctDNA assay tracking 319-1000 variants (median 1000 variants) to 114 plasma samples from 3 timepoints. Overall, ctDNA positivity was 100% at baseline, 79% at week 3 and 55% at week 12. Median tumor fraction (TFx) was 3.7 × 10 -4 (range 7.9 × 10 -7 -4.9 × 10 -1 ). TFx decreased 285-fold from baseline to week 3 in responders and 24-fold in non-responders. Week 12 ctDNA clearance correlated with RCB: clearance was observed in 10 of 11 patients with RCB 0, 3 of 8 with RCB 1, 4 of 15 with RCB 2 and 0 of 4 with RCB 3. Among six patients with known recurrence, five had persistent ctDNA at week 12. Conclusions: Neoadjuvant chemotherapy for TNBC reduced ctDNA TFx by 285-fold in responders and 24-fold in non-responders. In 58% (22/38) of patients, ctDNA TFx dropped below the detection level of a commercially available test, emphasizing the need for sensitive tests. Additional studies will determine whether ctDNA-guided approaches can improve outcomes. (Copyright © 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu