Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer

Abstract Preoperative staging of suspicious axillary lymph nodes (ALNs) allows patients to be triaged to ALN dissection or to sentinel lymph node biopsy (SLNB). Ultrasound-guided fine needle aspiration (FNA) and cytology of ALN is moderately sensitive but its clinical utility relies heavily on the c...

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Autores principales: Juanjuan Li, Bradley M. Downs, Leslie M. Cope, Mary Jo Fackler, Xiuyun Zhang, Chuan-gui Song, Christopher VandenBussche, Kejing Zhang, Yong Han, Yufei Liu, Suzana Tulac, Neesha Venkatesan, Timothy de Guzman, Chuang Chen, Edwin W. Lai, Jingping Yuan, Saraswati Sukumar
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:86a221899d2a40bf8a198d08bfddb6052021-12-02T15:23:18ZAutomated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer10.1038/s41523-021-00298-62374-4677https://doaj.org/article/86a221899d2a40bf8a198d08bfddb6052021-07-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00298-6https://doaj.org/toc/2374-4677Abstract Preoperative staging of suspicious axillary lymph nodes (ALNs) allows patients to be triaged to ALN dissection or to sentinel lymph node biopsy (SLNB). Ultrasound-guided fine needle aspiration (FNA) and cytology of ALN is moderately sensitive but its clinical utility relies heavily on the cytologist’s experience. We proposed that the 5-h automated GeneXpert system-based prototype breast cancer detection assay (BCDA) that quantitatively measures DNA methylation in ten tumor-specific gene markers could provide a facile, accurate test for detecting cancer in FNA of enlarged lymph nodes. We validated the assay in ALN-FNA samples from a prospective study of patients (N = 230) undergoing SLNB. In a blinded analysis of 218 evaluable LN-FNAs from 108 malignant and 110 benign LNs by histology, BCDA displayed a sensitivity of 90.7% and specificity of 99.1%, achieving an area under the ROC curve, AUC of 0.958 (95% CI: 0.928–0.989; P < 0.0001). Next, we conducted a study of archival FNAs of ipsilateral palpable LNs (malignant, N = 72, benign, N = 53 by cytology) collected in the outpatient setting prior to neoadjuvant chemotherapy (NAC). Using the ROC-threshold determined in the prospective study, compared to cytology, BCDA achieved a sensitivity of 94.4% and a specificity of 92.5% with a ROC-AUC = 0.977 (95% CI: 0.953–1.000; P < 0.0001). Our study shows that the automated assay detects cancer in suspicious lymph nodes with a high level of accuracy within 5 h. This cancer detection assay, scalable for analysis to scores of LN FNAs, could assist in determining eligibility of patients to different treatment regimens.Juanjuan LiBradley M. DownsLeslie M. CopeMary Jo FacklerXiuyun ZhangChuan-gui SongChristopher VandenBusscheKejing ZhangYong HanYufei LiuSuzana TulacNeesha VenkatesanTimothy de GuzmanChuang ChenEdwin W. LaiJingping YuanSaraswati SukumarNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-9 (2021)
institution DOAJ
collection DOAJ
language EN
topic Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Juanjuan Li
Bradley M. Downs
Leslie M. Cope
Mary Jo Fackler
Xiuyun Zhang
Chuan-gui Song
Christopher VandenBussche
Kejing Zhang
Yong Han
Yufei Liu
Suzana Tulac
Neesha Venkatesan
Timothy de Guzman
Chuang Chen
Edwin W. Lai
Jingping Yuan
Saraswati Sukumar
Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer
description Abstract Preoperative staging of suspicious axillary lymph nodes (ALNs) allows patients to be triaged to ALN dissection or to sentinel lymph node biopsy (SLNB). Ultrasound-guided fine needle aspiration (FNA) and cytology of ALN is moderately sensitive but its clinical utility relies heavily on the cytologist’s experience. We proposed that the 5-h automated GeneXpert system-based prototype breast cancer detection assay (BCDA) that quantitatively measures DNA methylation in ten tumor-specific gene markers could provide a facile, accurate test for detecting cancer in FNA of enlarged lymph nodes. We validated the assay in ALN-FNA samples from a prospective study of patients (N = 230) undergoing SLNB. In a blinded analysis of 218 evaluable LN-FNAs from 108 malignant and 110 benign LNs by histology, BCDA displayed a sensitivity of 90.7% and specificity of 99.1%, achieving an area under the ROC curve, AUC of 0.958 (95% CI: 0.928–0.989; P < 0.0001). Next, we conducted a study of archival FNAs of ipsilateral palpable LNs (malignant, N = 72, benign, N = 53 by cytology) collected in the outpatient setting prior to neoadjuvant chemotherapy (NAC). Using the ROC-threshold determined in the prospective study, compared to cytology, BCDA achieved a sensitivity of 94.4% and a specificity of 92.5% with a ROC-AUC = 0.977 (95% CI: 0.953–1.000; P < 0.0001). Our study shows that the automated assay detects cancer in suspicious lymph nodes with a high level of accuracy within 5 h. This cancer detection assay, scalable for analysis to scores of LN FNAs, could assist in determining eligibility of patients to different treatment regimens.
format article
author Juanjuan Li
Bradley M. Downs
Leslie M. Cope
Mary Jo Fackler
Xiuyun Zhang
Chuan-gui Song
Christopher VandenBussche
Kejing Zhang
Yong Han
Yufei Liu
Suzana Tulac
Neesha Venkatesan
Timothy de Guzman
Chuang Chen
Edwin W. Lai
Jingping Yuan
Saraswati Sukumar
author_facet Juanjuan Li
Bradley M. Downs
Leslie M. Cope
Mary Jo Fackler
Xiuyun Zhang
Chuan-gui Song
Christopher VandenBussche
Kejing Zhang
Yong Han
Yufei Liu
Suzana Tulac
Neesha Venkatesan
Timothy de Guzman
Chuang Chen
Edwin W. Lai
Jingping Yuan
Saraswati Sukumar
author_sort Juanjuan Li
title Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer
title_short Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer
title_full Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer
title_fullStr Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer
title_full_unstemmed Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer
title_sort automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/86a221899d2a40bf8a198d08bfddb605
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