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 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.