Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy

BackgroundPatients with stage II to III breast cancer have a high recurrence rate. The early detection of recurrent breast cancer remains a major unmet need. Circulating tumor DNA (ctDNA) has been proven to be a marker of disease progression in metastatic breast cancer. We aimed to evaluate the prog...

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Autores principales:	Po-Han Lin, Ming-Yang Wang, Chiao Lo, Li-Wei Tsai, Tzu-Chun Yen, Thomas Yoyan Huang, Wei-Chih Huang, Karen Yang, Chih-Kai Chen, Sheng-Chih Fan, Sung-Hsin Kuo, Chiun-Sheng Huang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	circulating tumor DNA neoadjuvant therapy breast cancer recurrence next-generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5c086e33a22b4ccca39c569b8be44274
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spelling	oai:doaj.org-article:5c086e33a22b4ccca39c569b8be442742021-11-12T05:00:48ZCirculating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy2234-943X10.3389/fonc.2021.736769https://doaj.org/article/5c086e33a22b4ccca39c569b8be442742021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.736769/fullhttps://doaj.org/toc/2234-943XBackgroundPatients with stage II to III breast cancer have a high recurrence rate. The early detection of recurrent breast cancer remains a major unmet need. Circulating tumor DNA (ctDNA) has been proven to be a marker of disease progression in metastatic breast cancer. We aimed to evaluate the prognostic value of ctDNA in the setting of neoadjuvant therapy (NAT).MethodsPlasma was sampled at the initial diagnosis (defined as before NAT) and after breast surgery and neoadjuvant therapy(defined as after NAT). We extracted ctDNA from the plasma and performed deep sequencing of a target gene panel. ctDNA positivity was marked by the detection of alterations, such as mutations and copy number variations.ResultsA total of 95 patients were enrolled in this study; 60 patients exhibited ctDNA positivity before NAT, and 31 patients exhibited ctDNA positivity after NAT. A pathologic complete response (pCR) was observed in 13 patients, including one ER(+)Her2(-) patient, six Her2(+) patients and six triple-negative breast cancer (TNBC) patients. Among the entire cohort, multivariate analysis showed that N3 classification and ctDNA positivity after NAT were independent risk factors that predicted recurrence (N3, hazard ratio (HR) 3.34, 95% confidence interval (CI) 1.26 – 8.87, p = 0.016; ctDNA, HR 4.29, 95% CI 2.06 – 8.92, p < 0.0001). The presence of ctDNA before NAT did not affect the rate of recurrence-free survival. For patients with Her2(+) or TNBC, patients who did not achieve pCR were associated with a trend of higher recurrence (p = 0.105). Advanced nodal status and ctDNA positivity after NAT were significant risk factors for recurrence (N2 – 3, HR 3.753, 95% CI 1.146 – 12.297, p = 0.029; ctDNA, HR 3.123, 95% CI 1.139 – 8.564, p = 0.027). Two patients who achieved pCR had ctDNA positivity after NAT; one TNBC patient had hepatic metastases six months after surgery, and one Her2(+) breast cancer patient had brain metastasis 13 months after surgery.ConclusionsThis study suggested that the presence of ctDNA after NAT is a robust marker for predicting relapse in stage II to III breast cancer patients.Po-Han LinPo-Han LinMing-Yang WangChiao LoLi-Wei TsaiTzu-Chun YenThomas Yoyan HuangWei-Chih HuangKaren YangChih-Kai ChenSheng-Chih FanSung-Hsin KuoChiun-Sheng HuangChiun-Sheng HuangFrontiers Media S.A.articlecirculating tumor DNAneoadjuvant therapybreast cancerrecurrencenext-generation sequencingNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	circulating tumor DNA neoadjuvant therapy breast cancer recurrence next-generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	circulating tumor DNA neoadjuvant therapy breast cancer recurrence next-generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Po-Han Lin Po-Han Lin Ming-Yang Wang Chiao Lo Li-Wei Tsai Tzu-Chun Yen Thomas Yoyan Huang Wei-Chih Huang Karen Yang Chih-Kai Chen Sheng-Chih Fan Sung-Hsin Kuo Chiun-Sheng Huang Chiun-Sheng Huang Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy
description	BackgroundPatients with stage II to III breast cancer have a high recurrence rate. The early detection of recurrent breast cancer remains a major unmet need. Circulating tumor DNA (ctDNA) has been proven to be a marker of disease progression in metastatic breast cancer. We aimed to evaluate the prognostic value of ctDNA in the setting of neoadjuvant therapy (NAT).MethodsPlasma was sampled at the initial diagnosis (defined as before NAT) and after breast surgery and neoadjuvant therapy(defined as after NAT). We extracted ctDNA from the plasma and performed deep sequencing of a target gene panel. ctDNA positivity was marked by the detection of alterations, such as mutations and copy number variations.ResultsA total of 95 patients were enrolled in this study; 60 patients exhibited ctDNA positivity before NAT, and 31 patients exhibited ctDNA positivity after NAT. A pathologic complete response (pCR) was observed in 13 patients, including one ER(+)Her2(-) patient, six Her2(+) patients and six triple-negative breast cancer (TNBC) patients. Among the entire cohort, multivariate analysis showed that N3 classification and ctDNA positivity after NAT were independent risk factors that predicted recurrence (N3, hazard ratio (HR) 3.34, 95% confidence interval (CI) 1.26 – 8.87, p = 0.016; ctDNA, HR 4.29, 95% CI 2.06 – 8.92, p < 0.0001). The presence of ctDNA before NAT did not affect the rate of recurrence-free survival. For patients with Her2(+) or TNBC, patients who did not achieve pCR were associated with a trend of higher recurrence (p = 0.105). Advanced nodal status and ctDNA positivity after NAT were significant risk factors for recurrence (N2 – 3, HR 3.753, 95% CI 1.146 – 12.297, p = 0.029; ctDNA, HR 3.123, 95% CI 1.139 – 8.564, p = 0.027). Two patients who achieved pCR had ctDNA positivity after NAT; one TNBC patient had hepatic metastases six months after surgery, and one Her2(+) breast cancer patient had brain metastasis 13 months after surgery.ConclusionsThis study suggested that the presence of ctDNA after NAT is a robust marker for predicting relapse in stage II to III breast cancer patients.
format	article
author	Po-Han Lin Po-Han Lin Ming-Yang Wang Chiao Lo Li-Wei Tsai Tzu-Chun Yen Thomas Yoyan Huang Wei-Chih Huang Karen Yang Chih-Kai Chen Sheng-Chih Fan Sung-Hsin Kuo Chiun-Sheng Huang Chiun-Sheng Huang
author_facet	Po-Han Lin Po-Han Lin Ming-Yang Wang Chiao Lo Li-Wei Tsai Tzu-Chun Yen Thomas Yoyan Huang Wei-Chih Huang Karen Yang Chih-Kai Chen Sheng-Chih Fan Sung-Hsin Kuo Chiun-Sheng Huang Chiun-Sheng Huang
author_sort	Po-Han Lin
title	Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy
title_short	Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy
title_full	Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy
title_fullStr	Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy
title_full_unstemmed	Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy
title_sort	circulating tumor dna as a predictive marker of recurrence for patients with stage ii-iii breast cancer treated with neoadjuvant therapy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5c086e33a22b4ccca39c569b8be44274
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Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy

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