Prognostic value of extranodal extension in axillary lymph node-positive breast cancer

Abstract Several studies have demonstrated that extranodal extension (ENE) is associated with prognosis in breast cancer. Whether this association should be described in pathological reports warrants further investigation. In this research, we evaluated the predictive value of ENE in axillary lymph...

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Autores principales:	XiaoXi Ma, Xia Yang, Wentao Yang, Ruohong Shui
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/04bf4a394ff54f93a5d6ad8581a43e53
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id	oai:doaj.org-article:04bf4a394ff54f93a5d6ad8581a43e53
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q XiaoXi Ma Xia Yang Wentao Yang Ruohong Shui Prognostic value of extranodal extension in axillary lymph node-positive breast cancer
description	Abstract Several studies have demonstrated that extranodal extension (ENE) is associated with prognosis in breast cancer. Whether this association should be described in pathological reports warrants further investigation. In this research, we evaluated the predictive value of ENE in axillary lymph nodes (ALNs) in invasive breast cancer and explored the feasibility of employing ENE to predict clinicopathological features, nodal burden, disease recurrence-free survival (DRFS) and overall survival (OS) in clinical practice. In addition, the cutoff values of perpendicular diameter ENE (PD-ENE) and circumferential diameter ENE (CD-ENE) of ENE were investigated. A total of 402 cases of primary invasive breast cancer were extracted from Fudan University Shanghai Cancer Center; these patients underwent axillary lymph node dissection (ALND) between 2010 and 2015. ENE in the ALN was defined as the tumor cells breaking through the lymph node capsule into peripheral adipose tissue and causing connective tissue reactions. Relationships between ENE and clinicopathological features, nodal burden, disease recurrence-free survival (DRFS) and overall survival (OS) were analyzed. PD-ENE was defined by measuring from the point where tumor tissue broke the node capsule to the highest point of the tumor cells in the perinodal adipose tissue.K The average PD-ENE was 1.8 mm; therefore, we divided ENE-positive patients into two groups: PD-ENE no greater than 2 mm and PD-ENE greater than 2 mm. CD-ENE was defined as measuring along the nodal capsule as the distance between peripheral edges of the ENE area. According to the average circumferential diameter (CD-ENE), we classified ENE-positive patients into two groups: CD-ENE no greater than 3 mm and CD-ENE greater than 3 mm. Correlations between ENE cutoffs and prognosis were analyzed. In this cohort of patients, 158 (39.3%) cases were positive for ENE in ALN.98 (24.4%) cases had PD-ENE no larger than 2 mm, and 60 (14.9%) cases had PD-ENE larger than 2 mm. Also, 112 (27.9%) cases had CD-ENE no larger than 3 mm, and 46 (11.4%) cases had CD-ENE larger than 3 mm. Statistical analysis indicated that histological grade, N stage, and HER2 overexpression subtype were associated with ENE. The presence of ENE had significant statistical correlations with nodal burden, including N stage, median metastatic tumor diameter and peri-lymph node vascular invasion (p < 0.001, p < 0.001, p = 0.001, respectively). Cox regression analysis demonstrated that patients with ENE exhibited significantly reduced DRFS in both univariable analysis (HR 2.126, 95% CI 1.453–3.112, p < 0.001) and multivariable analysis (HR 1.745, 95% CI 1.152–2.642, p = 0.009) compared with patients without ENE. For overall survival (OS), patients with ENE were associated with OS in univariable analysis (HR 2.505, 95% CI 1.337–4.693, p = 0.004) but not in multivariable analysis (HR 1.639, 95% CI 0.824–3.260, p = 0.159). Kaplan–Meier curves and log-rank test showed that patients with ENE in ALN had lower DRFS and OS (for DRFS: p < 0.0001; and for OS: p = 0.002, respectively). However, neither the PD-ENE group (divided by 2 mm) nor the CD-ENE group (divided by 3 mm) exhibited significant differences regarding nodal burden and prognosis. Our study indicated that ENE in the ALN was a predictor of prognosis in breast cancer. ENE was an independent prognostic factor for DRFS and was associated with OS. ENE in the ALN was associated with a higher nodal burden. The size of ENE, which was classified by a 3-mm (CD-ENE) or 2-mm (PD-ENE) cutoff value, had no significant prognostic value in this study. Based on our findings, the presence of ENE should be included in routine pathological reports of breast cancers. However, the cutoff values of ENE warrant further investigation.
format	article
author	XiaoXi Ma Xia Yang Wentao Yang Ruohong Shui
author_facet	XiaoXi Ma Xia Yang Wentao Yang Ruohong Shui
author_sort	XiaoXi Ma
title	Prognostic value of extranodal extension in axillary lymph node-positive breast cancer
title_short	Prognostic value of extranodal extension in axillary lymph node-positive breast cancer
title_full	Prognostic value of extranodal extension in axillary lymph node-positive breast cancer
title_fullStr	Prognostic value of extranodal extension in axillary lymph node-positive breast cancer
title_full_unstemmed	Prognostic value of extranodal extension in axillary lymph node-positive breast cancer
title_sort	prognostic value of extranodal extension in axillary lymph node-positive breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/04bf4a394ff54f93a5d6ad8581a43e53
work_keys_str_mv	AT xiaoxima prognosticvalueofextranodalextensioninaxillarylymphnodepositivebreastcancer AT xiayang prognosticvalueofextranodalextensioninaxillarylymphnodepositivebreastcancer AT wentaoyang prognosticvalueofextranodalextensioninaxillarylymphnodepositivebreastcancer AT ruohongshui prognosticvalueofextranodalextensioninaxillarylymphnodepositivebreastcancer
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spelling	oai:doaj.org-article:04bf4a394ff54f93a5d6ad8581a43e532021-12-02T14:49:25ZPrognostic value of extranodal extension in axillary lymph node-positive breast cancer10.1038/s41598-021-88716-42045-2322https://doaj.org/article/04bf4a394ff54f93a5d6ad8581a43e532021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88716-4https://doaj.org/toc/2045-2322Abstract Several studies have demonstrated that extranodal extension (ENE) is associated with prognosis in breast cancer. Whether this association should be described in pathological reports warrants further investigation. In this research, we evaluated the predictive value of ENE in axillary lymph nodes (ALNs) in invasive breast cancer and explored the feasibility of employing ENE to predict clinicopathological features, nodal burden, disease recurrence-free survival (DRFS) and overall survival (OS) in clinical practice. In addition, the cutoff values of perpendicular diameter ENE (PD-ENE) and circumferential diameter ENE (CD-ENE) of ENE were investigated. A total of 402 cases of primary invasive breast cancer were extracted from Fudan University Shanghai Cancer Center; these patients underwent axillary lymph node dissection (ALND) between 2010 and 2015. ENE in the ALN was defined as the tumor cells breaking through the lymph node capsule into peripheral adipose tissue and causing connective tissue reactions. Relationships between ENE and clinicopathological features, nodal burden, disease recurrence-free survival (DRFS) and overall survival (OS) were analyzed. PD-ENE was defined by measuring from the point where tumor tissue broke the node capsule to the highest point of the tumor cells in the perinodal adipose tissue.K The average PD-ENE was 1.8 mm; therefore, we divided ENE-positive patients into two groups: PD-ENE no greater than 2 mm and PD-ENE greater than 2 mm. CD-ENE was defined as measuring along the nodal capsule as the distance between peripheral edges of the ENE area. According to the average circumferential diameter (CD-ENE), we classified ENE-positive patients into two groups: CD-ENE no greater than 3 mm and CD-ENE greater than 3 mm. Correlations between ENE cutoffs and prognosis were analyzed. In this cohort of patients, 158 (39.3%) cases were positive for ENE in ALN.98 (24.4%) cases had PD-ENE no larger than 2 mm, and 60 (14.9%) cases had PD-ENE larger than 2 mm. Also, 112 (27.9%) cases had CD-ENE no larger than 3 mm, and 46 (11.4%) cases had CD-ENE larger than 3 mm. Statistical analysis indicated that histological grade, N stage, and HER2 overexpression subtype were associated with ENE. The presence of ENE had significant statistical correlations with nodal burden, including N stage, median metastatic tumor diameter and peri-lymph node vascular invasion (p < 0.001, p < 0.001, p = 0.001, respectively). Cox regression analysis demonstrated that patients with ENE exhibited significantly reduced DRFS in both univariable analysis (HR 2.126, 95% CI 1.453–3.112, p < 0.001) and multivariable analysis (HR 1.745, 95% CI 1.152–2.642, p = 0.009) compared with patients without ENE. For overall survival (OS), patients with ENE were associated with OS in univariable analysis (HR 2.505, 95% CI 1.337–4.693, p = 0.004) but not in multivariable analysis (HR 1.639, 95% CI 0.824–3.260, p = 0.159). Kaplan–Meier curves and log-rank test showed that patients with ENE in ALN had lower DRFS and OS (for DRFS: p < 0.0001; and for OS: p = 0.002, respectively). However, neither the PD-ENE group (divided by 2 mm) nor the CD-ENE group (divided by 3 mm) exhibited significant differences regarding nodal burden and prognosis. Our study indicated that ENE in the ALN was a predictor of prognosis in breast cancer. ENE was an independent prognostic factor for DRFS and was associated with OS. ENE in the ALN was associated with a higher nodal burden. The size of ENE, which was classified by a 3-mm (CD-ENE) or 2-mm (PD-ENE) cutoff value, had no significant prognostic value in this study. Based on our findings, the presence of ENE should be included in routine pathological reports of breast cancers. However, the cutoff values of ENE warrant further investigation.XiaoXi MaXia YangWentao YangRuohong ShuiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)

Prognostic value of extranodal extension in axillary lymph node-positive breast cancer

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