Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis

Abstract

Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta-analysis; they globally include 624 patients (163 ENE+ and 461 ENE-) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR = 2.51; 95% CI: 1.66-3.79, p < 0.0001, I(2) = 0%) and recurrence of disease (RR = 2.07, 95% CI: 1.38-3.10, p < 0.0001, I(2) = 0%). These findings recommend the consideration of ENE from the gross sampling to the histopathological evaluation, in perspectives to be validated and included in the oncologic staging.

Breast Cancer Metastasis to the Axillary Lymph Nodes: Are Changes to the Lymph Node “Soil” Localized or Systemic?

“…The presence of ENE in sentinel lymph nodes has been associated with metastasis in nonsentinel lymph nodes 11 and increased risk of recurrence and overall mortality. 12 In our data set, patients with ENE had significantly higher numbers of metastatic lymph nodes. Thus, migration of tumor cells out of the involved lymph nodes and into the perinodal space allows metastatic cells to disseminate between individual lymph nodes and, once inside a new lymph node, may illicit gene expression changes that promote metastatic growth.…”

Oncofetal gene SALL4 and prognosis in cancer: A systematic review with meta-analysis

“…Since many epithelial cancers are characterized by SALL4 reactivation, this gene should be considered for developing future targeted therapeutic strategies. Due to its prognostic value, SALL4 expression should be considered as potential marker in the next-generation histopathological diagnosis, hopefully by standardized IHC protocols, integrating cancer morphological features and molecular targets information [44–52]. …”

Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer

“…Patient prognosis is determined largely by stratification based on age, lymph node involvement, tumor grade, and tumor cell-surface expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) (2)(3)(4)(5)(6)(7). Early diagnosis and targeted therapies, both hormonal and immunologic, are critical for the effective treatment of ER-, PR-, and HER2-positive disease.…”