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Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response
PURPOSE: Accurate response assessment during neoadjuvant systemic treatment (NST) poses a clinical challenge. Therefore, a minimally invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions. EXPERIMENTAL DESIGN: We profiled...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for Cancer Research
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377752/ https://www.ncbi.nlm.nih.gov/pubmed/34862246 http://dx.doi.org/10.1158/1078-0432.CCR-21-3231 |
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author | Zhou, Qing Gampenrieder, Simon P. Frantal, Sophie Rinnerthaler, Gabriel Singer, Christian F. Egle, Daniel Pfeiler, Georg Bartsch, Rupert Wette, Viktor Pichler, Angelika Petru, Edgar Dubsky, Peter C. Bago-Horvath, Zsuzsanna Fesl, Christian Rudas, Margaretha Ståhlberg, Anders Graf, Ricarda Weber, Sabrina Dandachi, Nadia Filipits, Martin Gnant, Michael Balic, Marija Heitzer, Ellen |
author_facet | Zhou, Qing Gampenrieder, Simon P. Frantal, Sophie Rinnerthaler, Gabriel Singer, Christian F. Egle, Daniel Pfeiler, Georg Bartsch, Rupert Wette, Viktor Pichler, Angelika Petru, Edgar Dubsky, Peter C. Bago-Horvath, Zsuzsanna Fesl, Christian Rudas, Margaretha Ståhlberg, Anders Graf, Ricarda Weber, Sabrina Dandachi, Nadia Filipits, Martin Gnant, Michael Balic, Marija Heitzer, Ellen |
author_sort | Zhou, Qing |
collection | PubMed |
description | PURPOSE: Accurate response assessment during neoadjuvant systemic treatment (NST) poses a clinical challenge. Therefore, a minimally invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions. EXPERIMENTAL DESIGN: We profiled 93 genes in tissue from 193 patients with early breast cancer. Patient-specific assays were designed for 145 patients to track ctDNA during NST in plasma. ctDNA presence and levels were correlated with complete pathological response (pCR) and residual cancer burden (RCB) as well as clinicopathologic characteristics of the tumor to identify potential proxies for ctDNA release. RESULTS: At baseline, ctDNA could be detected in 63/145 (43.4%) patients and persisted in 25/63 (39.7%) patients at mid-therapy (MT) and 15/63 (23.8%) patients at the end of treatment. ctDNA detection at MT was significantly associated with higher RCB (OR = 0.062; 95% CI, 0.01–0.48; P = 0.0077). Of 31 patients with detectable ctDNA at MT, 30 patients (96.8%) were nonresponders (RCB II, n = 8; RCB III, n = 22) and only one patient responded to the treatment (RCB I). Considering all 145 patients with baseline (BL) plasma, none of the patients with RCB 0 and only 6.7% of patients with RCB I had ctDNA detectable at MT, whereas 30.6% and 29.6% of patients with RCB II/III, respectively, had a positive ctDNA result. CONCLUSIONS: Overall, our results demonstrate that the detection and persistence of ctDNA at MT may have the potential to negatively predict response to neoadjuvant treatment and identify patients who will not achieve pCR or be classified with RCB II/III. |
format | Online Article Text |
id | pubmed-9377752 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for Cancer Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-93777522023-01-05 Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response Zhou, Qing Gampenrieder, Simon P. Frantal, Sophie Rinnerthaler, Gabriel Singer, Christian F. Egle, Daniel Pfeiler, Georg Bartsch, Rupert Wette, Viktor Pichler, Angelika Petru, Edgar Dubsky, Peter C. Bago-Horvath, Zsuzsanna Fesl, Christian Rudas, Margaretha Ståhlberg, Anders Graf, Ricarda Weber, Sabrina Dandachi, Nadia Filipits, Martin Gnant, Michael Balic, Marija Heitzer, Ellen Clin Cancer Res Precision Medicine and Imaging PURPOSE: Accurate response assessment during neoadjuvant systemic treatment (NST) poses a clinical challenge. Therefore, a minimally invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions. EXPERIMENTAL DESIGN: We profiled 93 genes in tissue from 193 patients with early breast cancer. Patient-specific assays were designed for 145 patients to track ctDNA during NST in plasma. ctDNA presence and levels were correlated with complete pathological response (pCR) and residual cancer burden (RCB) as well as clinicopathologic characteristics of the tumor to identify potential proxies for ctDNA release. RESULTS: At baseline, ctDNA could be detected in 63/145 (43.4%) patients and persisted in 25/63 (39.7%) patients at mid-therapy (MT) and 15/63 (23.8%) patients at the end of treatment. ctDNA detection at MT was significantly associated with higher RCB (OR = 0.062; 95% CI, 0.01–0.48; P = 0.0077). Of 31 patients with detectable ctDNA at MT, 30 patients (96.8%) were nonresponders (RCB II, n = 8; RCB III, n = 22) and only one patient responded to the treatment (RCB I). Considering all 145 patients with baseline (BL) plasma, none of the patients with RCB 0 and only 6.7% of patients with RCB I had ctDNA detectable at MT, whereas 30.6% and 29.6% of patients with RCB II/III, respectively, had a positive ctDNA result. CONCLUSIONS: Overall, our results demonstrate that the detection and persistence of ctDNA at MT may have the potential to negatively predict response to neoadjuvant treatment and identify patients who will not achieve pCR or be classified with RCB II/III. American Association for Cancer Research 2022-02-15 2021-12-02 /pmc/articles/PMC9377752/ /pubmed/34862246 http://dx.doi.org/10.1158/1078-0432.CCR-21-3231 Text en ©2021 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
spellingShingle | Precision Medicine and Imaging Zhou, Qing Gampenrieder, Simon P. Frantal, Sophie Rinnerthaler, Gabriel Singer, Christian F. Egle, Daniel Pfeiler, Georg Bartsch, Rupert Wette, Viktor Pichler, Angelika Petru, Edgar Dubsky, Peter C. Bago-Horvath, Zsuzsanna Fesl, Christian Rudas, Margaretha Ståhlberg, Anders Graf, Ricarda Weber, Sabrina Dandachi, Nadia Filipits, Martin Gnant, Michael Balic, Marija Heitzer, Ellen Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response |
title | Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response |
title_full | Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response |
title_fullStr | Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response |
title_full_unstemmed | Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response |
title_short | Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response |
title_sort | persistence of ctdna in patients with breast cancer during neoadjuvant treatment is a significant predictor of poor tumor response |
topic | Precision Medicine and Imaging |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377752/ https://www.ncbi.nlm.nih.gov/pubmed/34862246 http://dx.doi.org/10.1158/1078-0432.CCR-21-3231 |
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