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Multicenter Study
. 2021 Jun;6(3):100151.
doi: 10.1016/j.esmoop.2021.100151. Epub 2021 May 10.

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

G Houvenaeghel  1 , A de Nonneville  2 , M Cohen  3 , N Chopin  4 , C Coutant  5 , F Reyal  6 , C Mazouni  7 , P Gimbergues  8 , A-S Azuar  9 , M-P Chauvet  10 , J-M Classe  11 , E Daraï  12 , A Martinez  13 , R Rouzier  14 , C T de Lara  15 , E Lambaudie  3 , J Barrou  3 , A Goncalves  2
Affiliations
Multicenter Study

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

G Houvenaeghel et al. ESMO Open. 2021 Jun.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02869607.

Keywords: breast cancer; micro-metastases; sentinel node; survival.

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Conflict of interest statement

Disclosure The authors have declared no conflicts of interest. Data sharing The data sets generated and/or analyzed during the current study are not publicly available, as the study has used clinical databases of 13 different comprehensive cancer centers in France (ClinicalTrials.govNCT02869607).

Figures

Figure 1
Figure 1
Survival results adjusted on tumor subtypes with distinction between pN0, pN0(i+), pN1mi, 1pN1, and more than 1pN1. (A) Overall survival. (B) Disease-free survival. (C) Metastasis-free survival.
Figure 2
Figure 2
Kaplan Meier estimates for propensity-score-matched population with distinction between pN0(i−), pN1mi, and pN1macro. (A) Overall survival. (B) Disease-free survival. (C) Metastasis-free survival.
Supplementary Figure S1
Supplementary Figure S1
Supplementary Figure S2
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Supplementary Figure S4
Supplementary Figure S4
See this image and copyright information in PMC

References

    1. Burstein H.J., Curigliano G., Loibl S. Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019. Ann Oncol. 2019;30(10):1541–1557. - PubMed
    1. Schwartz A.M., Henson D.E., Chen D., Rajamarthandan S. Histologic grade remains a prognostic factor for breast cancer regardless of the number of positive lymph nodes and tumor size: a study of 161 708 cases of breast cancer from the SEER program. Arch Pathol Lab Med. 2014;138(8):1048–1052. - PubMed
    1. Mohammed R.A.A., Martin S.G., Gill M.S., Green A.R., Paish E.C., Ellis I.O. Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences. Am J Surg Pathol. 2007;31(12):1825–1833. - PubMed
    1. Cianfrocca M. Prognostic and predictive factors in early-stage breast cancer. Oncologist. 2004;9(6):606–616. - PubMed
    1. Jafferbhoy S., McWilliams B. Clinical significance and management of sentinel node micrometastasis in invasive breast cancer. Clin Breast Cancer. 2012;12(5):308–312. - PubMed

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