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. 2023 Mar 6;9(1):10.
doi: 10.1038/s41523-023-00512-7.

ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease

Shane R Stecklein  1   2   3   4 , Bruce F Kimler  1 , Rachel Yoder  4 , Kelsey Schwensen  5 , Joshua M Staley  4 , Qamar J Khan  5 , Anne P O'Dea  5 , Lauren E Nye  5 , Manana Elia  5 , Jaimie Heldstab  5 , Trisha Home  4 , Stephen Hyter  2 , Kamilla Isakova  4 , Harsh B Pathak  2 , Andrew K Godwin  2   4 , Priyanka Sharma  6   7
Affiliations

ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease

Shane R Stecklein et al. NPJ Breast Cancer. .

Abstract

Triple-negative breast cancer (TNBC) patients with residual disease (RD) after neoadjuvant systemic therapy (NAST) are at high risk for recurrence. Biomarkers to risk-stratify patients with RD could help individualize adjuvant therapy and inform future adjuvant therapy trials. We aim to investigate the impact of circulating tumor DNA (ctDNA) status and residual cancer burden (RCB) class on outcomes in TNBC patients with RD. We analyze end-of-treatment ctDNA status in 80 TNBC patients with residual disease who are enrolled in a prospective multisite registry. Among 80 patients, 33% are ctDNA positive (ctDNA+) and RCB class distribution is RCB-I = 26%, RCB-II = 49%, RCB-III = 18% and 7% unknown. ctDNA status is associated with RCB status, with 14%, 31%, and 57% of patients within RCB-I, -II, and -III classes demonstrating ctDNA+ status (P = 0.028). ctDNA+ status is associated with inferior 3-year EFS (48% vs. 82%, P < 0.001) and OS (50% vs. 86%, P = 0.002). ctDNA+ status predicts inferior 3-year EFS among RCB-II patients (65% vs. 87%, P = 0.044) and shows a trend for inferior EFS among RCB-III patients (13% vs. 40%, P = 0.081). On multivariate analysis accounting for T stage and nodal status, RCB class and ctDNA status independently predict EFS (HR = 5.16, P = 0.016 for RCB class; HR = 3.71, P = 0.020 for ctDNA status). End-of-treatment ctDNA is detectable in one-third of TNBC patients with residual disease after NAST. ctDNA status and RCB are independently prognostic in this setting.

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Conflict of interest statement

A.P.O.: Consulting honoraria from Pfizer, Puma Biotechnology, Novartis, Daiichi Sankyo, Astra Zeneca, and Seattle Genetics; A.K.G.: Co-founder of Sinochips Diagnostics, serves as a scientific advisory board member to Biovica, Clara Biotech, and Sinochips Diagnostics, and receives research funding from Predicine and VITRAC Therapeutics; P.S.: Research funding from Novartis, Merck, Gilead, and BMS; serves as a consultant/advisor to AstraZeneca, Novartis, Merck, GSK, Pfizer, Sanofi, and Genzyme; and receives royalties from UpToDate. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Mutations detected in ctDNA are shown for individual patients, with variant allele frequencies and germline testing results.
Patient-level ctDNA mutations and variant allele thresholds.
Fig. 2
Fig. 2. Survival by ctDNA status.
a EFS among ctDNA− and ctDNA+ patients. b OS among ctDNA− and ctDNA+ patients. P value associated with HR is Cox univariate regression. Log-rank P is also provided.
Fig. 3
Fig. 3. Survival by ctDNA status within RCB classes.
a EFS among ctDNA− and ctDNA+ patients within RCB-II and RCB-III classes. b OS among ctDNA− and ctDNA+ patients within RCB-II and RCB-III classes. P value associated with HR is Cox univariate regression. Log-rank P is also provided.
See this image and copyright information in PMC

References

    1. Li X, et al. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res. Treat. 2017;161:279–287. doi: 10.1007/s10549-016-4059-6. - DOI - PubMed
    1. Liedtke C, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J. Clin. Oncol. 2008;26:1275–1281. doi: 10.1200/JCO.2007.14.4147. - DOI - PubMed
    1. Spring LM, et al. Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis. Clin. Cancer Res. 2020;26:2838–2848. doi: 10.1158/1078-0432.CCR-19-3492. - DOI - PMC - PubMed
    1. Masuda N, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N. Engl. J. Med. 2017;376:2147–2159. doi: 10.1056/NEJMoa1612645. - DOI - PubMed
    1. Mayer IA, et al. Randomized phase III postoperative trial of platinum-based chemotherapy versus capecitabine in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy: ECOG-ACRIN EA1131. J. Clin. Oncol. 2021;39:2539–2551. doi: 10.1200/JCO.21.00976. - DOI - PMC - PubMed