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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.

背景

淋巴结微转移（pN1mi）的预后影响在文献中存在争议。对于需要辅助治疗的患者，特别是对于内分泌受体（ER）阳性状态和 HER2 阴性肿瘤患者，需要明确这一点，因为基因表达谱的泛化在其推荐算法中使用了 pN 状态。

患者和方法

我们回顾性分析了 1999 年至 2014 年 13 个法国癌症中心治疗的 13773 例 ER 阳性乳腺癌患者。定义了 5 类腋窝淋巴结（LN）状态：阴性 LN（pN0i-）、孤立肿瘤细胞[pN0（i+）]、pN1mi 和 pN1 分为单（pN1=1）和多（pN1>1）个宏转移（>2mm）。根据肿瘤亚型，在整个患者队列和临床相关亚组中研究了 LN 微转移对结局的影响。采用倾向评分匹配来平衡与 pN 状态相关的已知预后变量的差异。

结果

通过前哨淋巴结活检确定，9427 例患者为 pN0（68.4%），546 例 pN0（i+）（4.0%），1446 例 pN1mi（10.5%）和 2354 例 pN1 有宏转移（17.1%）。中位随访 61.25 个月后，pN1 状态但不是 pN1mi 显著影响总生存期（OS）、无病生存期（DFS）、无转移生存期（MFS）和乳腺癌特异性生存期。在已知肿瘤亚型的患者亚组中，pN1=1（与 pN1>1 一样），但不是 pN1mi，对 OS 有显著的预后影响。DFS 和 MFS 仅受 pN1>1 的影响。在 luminal A 样肿瘤（n=7101）的亚组中观察到类似的结果。在匹配人群分析中，pN1macro，但不是 pN1mi，对 MFS 和 OS 有统计学上显著的负面影响。