Clinical significance of intramammary lymph nodes in female primary breast cancer: a systematic review and meta-analysis

Abstract

Intramammary lymph nodes (IntraMLNs), located within the breast parenchyma or axillary tail, are uncommon, and their clinical significance in primary breast cancer remains unclear. This meta-analysis evaluated the association between IntraMLN and axillary lymph node (ALN) status, together with incidence, metastatic rate, diagnostic performance, risk factors, and prognosis. PubMed, Embase, and the Cochrane Library were searched without language or date restrictions. Eligible studies included adult women with primary breast cancer and pathologically confirmed IntraMLNs. Data extraction and quality assessment were performed independently. Pooled proportions, odds ratios (ORs), and diagnostic test accuracy indices were estimated using fixed- or random-effects models. Publication bias was assessed using Egger’s or Deeks’ test. The review was registered in PROSPERO (CRD420251137541). Twenty-four studies involving 1,482 patients were included. The pooled incidence of pathologically detected IntraMLNs was 0.03 (95% CI, 0.01–0.08), and the metastatic rate was 0.32 (95% CI, 0.27–0.37). IntraMLN positivity was significantly associated with ALN involvement (pooled OR, 4.96; 95% CI, 3.55–6.93). Pooled sensitivity, specificity, PPV, NPV, PLR, NLR, and DOR were 0.505, 0.813, 0.674, 0.711, 2.738, 0.635, and 4.961, respectively. Lymphovascular invasion, tumor size/T stage, and histological grade were commonly associated with IntraMLN metastasis. Prognostic findings were inconsistent. IntraMLN metastasis is strongly associated with ALN involvement and indicates increased axillary metastatic risk. However, its diagnostic accuracy is insufficient to replace standard axillary staging, and its independent prognostic value remains inconclusive.