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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Circulating tumor DNA association with residual cancer burden after neoadjuvant chemotherapy in triple-negative breast cancer in TBCRC 030
Annals of Oncology, Volume 34, No. 10, Year 2023
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Description
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. © 2023 European Society for Medical Oncology
Authors & Co-Authors
Brufsky, Adam M.
United States, Pittsburgh
University of Pittsburgh School of Medicine
Traina, Tiffany A.
United States, New York
Memorial Sloan-kettering Cancer Center
Carey, Lisa A.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Rimawi, Mothaffar F.
United States, Houston
Baylor College of Medicine
Stearns, Vered
United States, Baltimore
The Sidney Kimmel Comprehensive Cancer Center
Falkson, Carla Isadora
United States, Birmingham
The University of Alabama at Birmingham
Burstein, Harold J.
United States, Boston
Dana-farber Cancer Institute
United States, Boston
Dana-farber/brigham and Women's Cancer Center
United States, Boston
Harvard Medical School
Winer, Eric P.Manuela
United States, Boston
Dana-farber Cancer Institute
United States, Boston
Dana-farber/brigham and Women's Cancer Center
United States, Boston
Harvard Medical School
Tayob, Nabihah
United States, Boston
Dana-farber Cancer Institute
Krop, Ian E.
United States, Boston
Dana-farber Cancer Institute
United States, Boston
Dana-farber/brigham and Women's Cancer Center
United States, Boston
Harvard Medical School
Makrigiorgos, Gerassimos Mike
United States, Boston
Dana-farber Cancer Institute
Statistics
Citations: 4
Authors: 11
Affiliations: 13
Identifiers
Doi:
10.1016/j.annonc.2023.08.004
ISSN:
09237534
Research Areas
Cancer
Genetics And Genomics
Study Design
Cohort Study
Case-Control Study