Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer

Aziz, Sura; Wik, Elisabeth; Knutsvik, Gøril; Klingen, Tor Audun; Chen, Ying; Davidsen, Benedicte; Aas, Hans; Aas, Turid; Akslen, Lars A.

doi:10.1371/journal.pone.0171853

Cited by 25 publications

(18 citation statements)

References 22 publications

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“…In this study, tumor size, as well as higher histologic grades, were negatively correlated with the survival rates 8,13,14,18 . Our results, showing that both the number of positive ALNs and the presence of LVI have a negative impact on the survival rates, are in line with previously published data [32][33][34][35][36] . In concordance with former observations, BC molecular subtype also affected survival 12,24,31 .…”

Section: Discussionsupporting

confidence: 93%

“…Although a negative impact of ENE in SLNs on survival has been suggested 34 , we observed none. Nevertheless, in our patients with ENE-positive SLNs, higher nodal stages (pN2-pN3) were more frequent and non-sentinel ALNs were more often positive compared to the patients with macrometastatic, ENE-negative SLNs, indicating that ENE in SLNs affects survival indirectly, which is in accordance with the findings of Schwentner L et al 38 .…”

Section: Discussioncontrasting

confidence: 90%

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Impact of HER2 receptor status on axillary nodal burden in patients with non-luminal A invasive ductal breast carcinoma

et al. 2019

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Background: Breast cancer (BC) is the most common malignancy in women. Aim: To assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST) both at diagnosis and during the 4-year postoperative period. Patients and Methods: We retrospectively included 375 women with an early clinical stage of non-luminal IDC-NST who between 2007 and 2013 underwent breast surgery at a clinical hospital. They were divided into phenotype-based groups: HR+HER2-, HR+HER2+, HR-HER2+ and HR-HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. If > 3 ALNs were positive, radiotherapy was delivered. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy. Results: Larger tumor size, higher grade, HR+, HER2+ status, and lymphovascular invasion (LVI) were predictive for ALN metastases at diagnosis. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were found in the HR-HER2-group, while the poorest locoregional recurrence-free survival (LRFS) was observed in HR-HER2+ and HR-HER2-groups. HER2 status was not predictor of survival. Conclusions: HER2+ status was predictive for ALN involvement at diagnosis but had no effect on 4-year LRFS in these patients.

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 90%

Impact of HER2 receptor status on axillary nodal burden in patients with non-luminal A invasive ductal breast carcinoma

et al. 2019

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“…Given how common ENE is in cSCCHN, sub-stratification of ENE by disease extent may provide prognostic utility, similar to the correlation between increasing ENE extent and nodal tumor burden with disease recurrence in lymph node positive breast cancer. 32,33 This study has several limitations, including its retrospective design which may lead to bias in the results because higher stage disease may have been treated more aggressively. However, during the study period, management of metastatic cSCCHN was reasonably standardized in our unit in terms of preoperative imaging, approach to surgery, the routine administration of adjuvant radiotherapy in the majority of patients and the rare use of concurrent chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…The poor performance of AJCC7 and AJCC8 in our population highlights the need for a new risk stratification system specific to cSCCHN. Given how common ENE is in cSCCHN, sub‐stratification of ENE by disease extent may provide prognostic utility, similar to the correlation between increasing ENE extent and nodal tumor burden with disease recurrence in lymph node positive breast cancer …”

Section: Discussionmentioning

confidence: 99%

A critical analysis of the prognostic performance of the 8th edition American Joint Committee on Cancer staging for metastatic cutaneous squamous cell carcinoma of the head and neck

et al. 2019

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Background The 8th edition AJCC staging of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) incorporated extranodal extension (ENE) for the first time. This study compared the prognostic performance of the 7th and 8th edition staging for cSCCHN with nodal metastases. Methods Retrospective analysis of 96 patients with metastatic cSCCHN, comparing the ability of staging systems to predict disease‐specific and overall survival (OS) using the proportion of variation explained and Harrell's C‐index. Results In AJCC8, the N classification was upstaged in 77% of patients due to the presence of ENE and 88% of patients were classified as TNM stage IV. AJCC8 was inferior to AJCC7 in predicting disease‐specific survival for both N and TNM stages, and OS by TNM stage. Conclusions The majority of patients with metastatic cSCCHN have ENE and are classified as TNM stage IV based on the 8th edition staging, resulting in poor prognostic performance.

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“…Methodologies for ENE size measurement is still not standardized [40,44,46] . Aziz et al evaluated the clinical significance of ENE which was divided into circumferential (CD-ENE) and perpendicular (PD-ENE) extra-nodal growth, and the results showed that PD-ENE (with 3mm as cut-off value) was an independent prognostic factor for disease-free survival of breast cancers [48] . Choi et al and Gooch et al's study showed that the extent of ENE was associated with greater axillary disease burden, and ENE >2mm was the strongest predictor of N2 disease (p < 0.001), and poorer DFS and OS [25,39] .…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of extranodal extension in sentinel lymph node positive breast cancers

Yang

et al. 2020

Preprint

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Background The precise stage of lymph node (LN) metastasis is a strong prognostic factor in breast cancer, and sentinel lymph node (SLN) is the first station of nodal metastasis, whereas the clinical value of extranodal extension (ENE) in SLN are still in exploration.Objective Our study aimed to evaluate the predictive and prognostic values of ENE in SLN and to investigate the feasibility of ENE to predict non-SLN metastasis, disease free survival (DFS) and overall survival (OS) in clinical practice.Methods 183 cases of primary invasive breast cancer (cT1-2N0 breast cancer with 1-2 positive SLNs) underwent SLN biopsy and axillary lymph node dissection (ALND) between 2008 and 2015 were extracted from the pathology database of Fudan University Shanghai Cancer Center. Sections were reviewed for the microscopic features of SLN, including the number and pattern of SLN metastasis, SLNs positive ratio, nodal vascular invasion (NVI), and ENE. The associations between tumor features including ENE and non-SLN metastasis, DFS and OS were analyzed. Moreover, ENE was subclassified into circumferential (CD-ENE) and perpendicular (PD-ENE) and set a threshold as 2mm or 3mm to evaluate the prognostic value of ENE.Results 73/183 (39.9 %) cases were positive for ENE in SLN. Logistic regression analysis indicated that ENE, the number and pattern of SLN involvement, SLN positive ratio, and NVI were significantly associated with the presence of non-SLN metastasis in univariate analysis. ENE, higher number of SLN involvement, SLN macrometastasis, and NVI were significantly associated with a higher rate of non-SLN metastasis in multivariate analysis. Cox regression analysis showed ENE in SLN was associated with DFS and OS in univariable analysis, but not in multivariable analysis. Whereas the size of ENE (CD-ENE and PD-ENE) subdivided by 3mm (or 2mm) cutoff values were not found as strongly prognostic factors of DFS and OS as well.Conclusions Our study indicated that ENE in SLN was a predictor for non-SLN metastasis in breast cancers, patients with ENE in SLN had a higher rate of non-SLN metastasis. ENE in SLN was associated with DFS and OS in univariable analysis, but not in multivariable analysis. The size of ENE (CD-ENE and PD-ENE) which was classified by a 3mm (or 2mm) cutoff value had no significant prognostic values in this study. The prognostic value of ENE in SLN and the cutoff values of ENE in SLN in breast cancers need further investigation.

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Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer

Cited by 25 publications

References 22 publications

Impact of HER2 receptor status on axillary nodal burden in patients with non-luminal A invasive ductal breast carcinoma

Impact of HER2 receptor status on axillary nodal burden in patients with non-luminal A invasive ductal breast carcinoma

A critical analysis of the prognostic performance of the 8th edition American Joint Committee on Cancer staging for metastatic cutaneous squamous cell carcinoma of the head and neck

Clinical significance of extranodal extension in sentinel lymph node positive breast cancers

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