ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease
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 inv...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-03-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-023-00512-7 |
| _version_ | 1797426516560183296 |
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| author | Shane R. Stecklein Bruce F. Kimler Rachel Yoder Kelsey Schwensen Joshua M. Staley Qamar J. Khan Anne P. O’Dea Lauren E. Nye Manana Elia Jaimie Heldstab Trisha Home Stephen Hyter Kamilla Isakova Harsh B. Pathak Andrew K. Godwin Priyanka Sharma |
| author_facet | Shane R. Stecklein Bruce F. Kimler Rachel Yoder Kelsey Schwensen Joshua M. Staley Qamar J. Khan Anne P. O’Dea Lauren E. Nye Manana Elia Jaimie Heldstab Trisha Home Stephen Hyter Kamilla Isakova Harsh B. Pathak Andrew K. Godwin Priyanka Sharma |
| author_sort | Shane R. Stecklein |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T08:31:22Z |
| format | Article |
| id | doaj.art-00318f24d99f4b07bfee5dde9a0b9a2e |
| institution | Directory Open Access Journal |
| issn | 2374-4677 |
| language | English |
| last_indexed | 2024-03-09T08:31:22Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj.art-00318f24d99f4b07bfee5dde9a0b9a2e2023-12-02T19:32:21ZengNature Portfolionpj Breast Cancer2374-46772023-03-01911810.1038/s41523-023-00512-7ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual diseaseShane R. Stecklein0Bruce F. Kimler1Rachel Yoder2Kelsey Schwensen3Joshua M. Staley4Qamar J. Khan5Anne P. O’Dea6Lauren E. Nye7Manana Elia8Jaimie Heldstab9Trisha Home10Stephen Hyter11Kamilla Isakova12Harsh B. Pathak13Andrew K. Godwin14Priyanka Sharma15Department of Radiation Oncology, University of Kansas Medical CenterDepartment of Radiation Oncology, University of Kansas Medical CenterThe University of Kansas Cancer Center, University of Kansas Medical CenterDivision of Medical Oncology, Department of Internal Medicine, University of Kansas Medical CenterThe University of Kansas Cancer Center, University of Kansas Medical CenterDivision of Medical Oncology, Department of Internal Medicine, University of Kansas Medical CenterDivision of Medical Oncology, Department of Internal Medicine, University of Kansas Medical CenterDivision of Medical Oncology, Department of Internal Medicine, University of Kansas Medical CenterDivision of Medical Oncology, Department of Internal Medicine, University of Kansas Medical CenterDivision of Medical Oncology, Department of Internal Medicine, University of Kansas Medical CenterThe University of Kansas Cancer Center, University of Kansas Medical CenterDepartment of Pathology and Laboratory Medicine, University of Kansas Medical CenterThe University of Kansas Cancer Center, University of Kansas Medical CenterDepartment of Pathology and Laboratory Medicine, University of Kansas Medical CenterDepartment of Pathology and Laboratory Medicine, University of Kansas Medical CenterThe University of Kansas Cancer Center, University of Kansas Medical CenterAbstract 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.https://doi.org/10.1038/s41523-023-00512-7 |
| spellingShingle | Shane R. Stecklein Bruce F. Kimler Rachel Yoder Kelsey Schwensen Joshua M. Staley Qamar J. Khan Anne P. O’Dea Lauren E. Nye Manana Elia Jaimie Heldstab Trisha Home Stephen Hyter Kamilla Isakova Harsh B. Pathak Andrew K. Godwin Priyanka Sharma ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease npj Breast Cancer |
| title | ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease |
| title_full | ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease |
| title_fullStr | ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease |
| title_full_unstemmed | ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease |
| title_short | ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease |
| title_sort | ctdna and residual cancer burden are prognostic in triple negative breast cancer patients with residual disease |
| url | https://doi.org/10.1038/s41523-023-00512-7 |
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