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Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort(☆)

BACKGROUND: Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is fu...

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Autores principales: Houvenaeghel, G., de Nonneville, A., Cohen, M., Chopin, N., Coutant, C., Reyal, F., Mazouni, C., Gimbergues, P., Azuar, A.-S., Chauvet, M.-P., Classe, J.-M., Daraï, E., Martinez, A., Rouzier, R., de Lara, C.T., Lambaudie, E., Barrou, J., Goncalves, A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314870/
https://www.ncbi.nlm.nih.gov/pubmed/33984674
http://dx.doi.org/10.1016/j.esmoop.2021.100151
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author Houvenaeghel, G.
de Nonneville, A.
Cohen, M.
Chopin, N.
Coutant, C.
Reyal, F.
Mazouni, C.
Gimbergues, P.
Azuar, A.-S.
Chauvet, M.-P.
Classe, J.-M.
Daraï, E.
Martinez, A.
Rouzier, R.
de Lara, C.T.
Lambaudie, E.
Barrou, J.
Goncalves, A.
author_facet Houvenaeghel, G.
de Nonneville, A.
Cohen, M.
Chopin, N.
Coutant, C.
Reyal, F.
Mazouni, C.
Gimbergues, P.
Azuar, A.-S.
Chauvet, M.-P.
Classe, J.-M.
Daraï, E.
Martinez, A.
Rouzier, R.
de Lara, C.T.
Lambaudie, E.
Barrou, J.
Goncalves, A.
author_sort Houvenaeghel, G.
collection PubMed
description BACKGROUND: Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm. PATIENTS AND METHODS: We retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i−), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status. RESULTS: As determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS. CONCLUSION: LN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0.
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spelling pubmed-83148702021-07-31 Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort(☆) Houvenaeghel, G. de Nonneville, A. Cohen, M. Chopin, N. Coutant, C. Reyal, F. Mazouni, C. Gimbergues, P. Azuar, A.-S. Chauvet, M.-P. Classe, J.-M. Daraï, E. Martinez, A. Rouzier, R. de Lara, C.T. Lambaudie, E. Barrou, J. Goncalves, A. ESMO Open Original Research BACKGROUND: Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm. PATIENTS AND METHODS: We retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i−), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status. RESULTS: As determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS. CONCLUSION: LN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0. Elsevier 2021-05-10 /pmc/articles/PMC8314870/ /pubmed/33984674 http://dx.doi.org/10.1016/j.esmoop.2021.100151 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Houvenaeghel, G.
de Nonneville, A.
Cohen, M.
Chopin, N.
Coutant, C.
Reyal, F.
Mazouni, C.
Gimbergues, P.
Azuar, A.-S.
Chauvet, M.-P.
Classe, J.-M.
Daraï, E.
Martinez, A.
Rouzier, R.
de Lara, C.T.
Lambaudie, E.
Barrou, J.
Goncalves, A.
Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort(☆)
title Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort(☆)
title_full Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort(☆)
title_fullStr Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort(☆)
title_full_unstemmed Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort(☆)
title_short Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort(☆)
title_sort lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort(☆)
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314870/
https://www.ncbi.nlm.nih.gov/pubmed/33984674
http://dx.doi.org/10.1016/j.esmoop.2021.100151
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