Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study

Liikanen, Jenni S.; Leidenius, Marjut; Joensuu, Heikki; Vironen, Jaana; Meretoja, Tuomo J.

doi:10.1038/s41416-018-0052-7

Cited by 21 publications

(12 citation statements)

References 31 publications

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“…Our observations show that lymph node involvement is not dependent on the degree of tumor differentiation. Our findings confirm the observations of Tullberg et al concerning luminal A cancer [ 46 ] as well as studies conducted in breast cancers regardless of their molecular subtype [ 47 ]. On the contrary, Van Calster et al showed that tumor grade correlates with lymph node involvement in all subtypes of breast cancer [ 44 ].…”

Section: Discussionsupporting

confidence: 93%

“…Our study showed that patient age does not correlate with lymph node involvement in this molecular subtype. These results are confirmed by other authors [ 33 , 46 , 47 ]. Surprisingly, Van Calster et al showed that the increase of patient age by 10 years reduces the chance of nodal involvement [ 44 ].…”

Section: Discussionsupporting

confidence: 92%

“…The associations between pN stage and both tumor size and T stage were shown in ER-positive/HER2negative BC by Noda et al [33]. Several other authors have obtained similar results [45], but some did not show any relationships between tumor size and lymph node involvement in luminal A BC [46]. Our study showed that patient age does not correlate with lymph node involvement in this molecular subtype.…”

Section: Discussionsupporting

confidence: 75%

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Nodal status in luminal A invasive breast cancer: relationships with cytotoxic CD8 + and regulatory FOXP3 + cells tumor-associated infiltrate and other prognostic factors

et al. 2021

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Luminal A breast cancers are generally associated with low metastatic potential and good prognosis. However, there is a proportion of patients, who present with metastases in lymph nodes. The aim of our study was to determine the association between the number of positive lymph nodes and infiltrates of tumor-associated cytotoxic CD8 + (CTLs), regulatory FOXP3 + T cells (Tregs), as well as other prognostic factors. Immunohistochemistry (IHC) for CD8 + and FOXP3 + was performed in 87 formalin-fixed paraffin-embedded primary breast cancer tissues, and cell infiltrate was assessed under light microscope. We observed that node-positive cases were associated with higher numbers of Treg cells and lower CTL/Treg ratio. There was also an inverse correlation between the CTL/Treg ratio and the number of metastatic lymph nodes. Similar relationships were found between the number of metastatic lymph nodes and Treg density or CTL/Treg ratio in pT1 BC. An elevated intratumoral CTL/Treg ratio was associated with pN0 stage. The relationship between lymphovascular invasion (LVI) and Treg density was also noted in node-negative tumors. In addition, more advanced nodal stage was related to LVI, higher pT, and lower PR expression. The numbers of CD8 + and FOXP3 + were also associated with tumor size, histologic grade, PR expression, and mitotic index. The results of our study suggested that the levels of tumor-infiltrating regulatory and cytotoxic cells as well as the balance between them play a role in lymphovascular spread of luminal A breast cancers.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 75%

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Nodal status in luminal A invasive breast cancer: relationships with cytotoxic CD8 + and regulatory FOXP3 + cells tumor-associated infiltrate and other prognostic factors

et al. 2021

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“…The main advantage of this immunochemical method is to facilitate isolated tumor cell detection (<0.2 mm in diameter or 200 cells): isolated tumor cell detection increased by 35.2% when compared with histological examination according to Coleto et al (20). A recent prospective study of 936 pT1N0M0 breast cancer patients confirmed that isolated tumor cells in the sentinel lymph node were associated with unfavorable survival, justifying their detection by cytokeratin immunohistochemistry (40). In the present study, we defined positive nodal stage (pN+) by the presence of isolated tumor cells, micrometastases or macrometastases, whereas the pathologic nodal stage of breast cancer is still pN0 when only isolated tumor cells are present within the sentinel lymph node (18).…”

Section: Discussionmentioning

confidence: 99%

Proposal for a Histological Staging System of Mammary Carcinomas in Dogs and Cats. Part 1: Canine Mammary Carcinomas

et al. 2019

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Background: Staging of mammary carcinomas of dogs and cats is not only important for prognostic purposes, but also to guide therapy, in particular regarding adjuvant chemotherapy. The classical staging system relies on T, the clinical tumor size, N, the clinical nodal stage, and M, distant metastasis, evaluated by the clinician. However, a more precise and reliable staging system is applied to human stage I–III breast cancer, i.e., without distant metastasis, in which T is replaced by the pathologic tumor size (pT), and N is replaced by the pathologic nodal stage (pN), both evaluated by the pathologist. This staging system is strongly associated with patient outcomes, and is used to select treatment options. The purpose of this study was to design a histologic staging system for Canine Mammary Carcinomas (CMCs, part 1 of this article), and Feline Mammary Carcinomas (part 2), inspired from human oncology, and to assess its association with patient outcomes.Materials and Methods: This retrospective study included 433 female dogs with a surgically removed CMC. Patient outcomes were recorded over a 2-years follow up period. CMCs were staged according to pT (greatest diameter in millimeters on histological slides), lymphovascular invasion (LVI), and pN (confirmed by cytokeratin AE1/AE3 immunohistochemistry). The histological stages were defined as: Stage 0 (CMCs in situ, surrounded by a continuous layer of p63+ myoepithelial cells), Stage I (pT1 ≤ 20 mm, LVI–, pN0–pNX, where pNX refers to the absence of lymph node sample), Stage II (pT2 > 20 mm, LVI–, pN0–pNX), Stage IIIA (pT1, LVI+, and/or pN+), and Stage IIIB (pT2, LVI+, and/or pN+).Results: Disease-free-interval, overall survival and specific survival significantly differed by histological stage. For specific survival, median survival times and hazard ratios (HR) by Cox proportional hazards regression (p < 0.0001) were: Stage 0 (median survival not reached; HR = 1.00; N = 89; 21% of the dogs), Stage I (1,720 days; HR = 3.05; p = 0.0018; N = 81; 19%), Stage II (1,181 days; HR = 4.39; p < 0.0001; N = 79; 18%), Stage IIIA (348 days; HR = 10.59; p < 0.0001; N = 79; 18%), and Stage IIIB (163 days; HR = 16.59; p < 0.0001; N = 105; 24%).Conclusion: The proposed histological staging system (invasiveness, pT, LVI, pN) is a very strong prognostic factor for CMCs.

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“…Due to the lack of large multicenter randomized controlled clinical study and long follow-up time, the impact of ITCs on patients' survival is controversial. Some studies showed that ITCs had little effect on prognosis (3)(4)(5)(6)(7)(8)(9), while other researches suggested that ITCs had an adverse influence on survival (10)(11)(12)(13)(14)(15). Therefore, more studies are urgently needed to confirm the realworld curative effect of lymph node ITCs in patients with female breast cancer (FBC).…”

Section: Introductionmentioning

confidence: 99%

A Competing Risk Analysis Model to Determine the Prognostic Value of Isolated Tumor Cells in Axillary Lymph Nodes for T1N0M0 Breast Cancer Patients Based on the Surveillance, Epidemiology, and End Results Database

Zhang

et al. 2020

Front. Oncol.

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Introduction: Knowledge of the association between isolated tumor cells (ITCs) in breast cancer patients and the outcome is very limited. We aimed to determine the prognostic value of axillary lymph node ITCs for T1N0M0 female breast cancer (FBC) patients. Methods: Data for T1N0M0 FBC patients staged ITCs negative [pN0(i−)] and positive [pN0(i+)] were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. Prognostic predictors were identified by Kaplan-Meier analysis, competing risk model, and Fine-Gray multivariable regression model. Results: A total of 94,599 subjects were included, 88,632 of whom were staged at pN0(i−) and 5,967 were pN0(i+). Patients staged pN0(i+) had worse breast cancerspecific survival (BCSS) [hazard ratio (HR): 1.298, 95% CI = 1.069-1.576, P = 0.003] and higher breast cancer-specific death (BCSD) rate (Gray's test, P = 0.002) than pN0(i−) group. In the Fine-Gray multivariable regression analysis, the pN0(i+) group had higher BCSD rate (HR: 1.321, 95% CI = 1.109-1.575, P = 0.002) than pN0(i−) group. In subgroup analyses, no significant difference in BCSD was shown between the chemotherapy and non-chemotherapy subgroup (Gray's test, P = 0.069) or radiotherapy and non-radiotherapy subgroup (Gray's test, P = 0.096). Conclusion: ITC was independently related to the increase of the BCSD rate and could be identified as a reliable survival predictor for T1N0M0 FBC patients.

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Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study

Abstract: We conclude that presence of ITCs in the SNs is an adverse prognostic factor in early small node-negative breast cancer, and may be considered in the decision-making for adjuvant therapy.

Cited by 21 publications

References 31 publications

Nodal status in luminal A invasive breast cancer: relationships with cytotoxic CD8 + and regulatory FOXP3 + cells tumor-associated infiltrate and other prognostic factors

Nodal status in luminal A invasive breast cancer: relationships with cytotoxic CD8 + and regulatory FOXP3 + cells tumor-associated infiltrate and other prognostic factors

Proposal for a Histological Staging System of Mammary Carcinomas in Dogs and Cats. Part 1: Canine Mammary Carcinomas

A Competing Risk Analysis Model to Determine the Prognostic Value of Isolated Tumor Cells in Axillary Lymph Nodes for T1N0M0 Breast Cancer Patients Based on the Surveillance, Epidemiology, and End Results Database

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