Clinicopathological characteristics and factors associated with axillary lymph node metastasis in multifocal/multicentric versus unifocal breast cancer: a retrospective study

Multifocal/multicentric breast cancer (MMBC) may exhibit a greater tumor burden and higher risk of lymph node involvement than unifocal breast cancer (UFBC). This study compared the clinicopathological characteristics and nodal positivity patterns of MMBC and UFBC and explored factors associated with axillary lymph node (ALN) metastasis.

This retrospective single-center study included 66 patients with MMBC and 104 patients with UFBC treated between October 2017 and March 2020. Clinicopathological characteristics and sentinel lymph node and ALN positivity rates were compared between groups. Factors associated with ALN metastasis were evaluated separately in each group. Variables significant in univariate analyses were included in Firth-type bias-reduced logistic regression models. Exploratory nomograms were constructed, and model performance was assessed using the area under the receiver operating characteristic curve (AUC), Brier score, calibration analysis, and bootstrap internal validation.

Compared with UFBC, MMBC was associated with higher proportions of patients aged ≤50 years (53.03% vs. 36.54%; P = 0.034), lymphovascular invasion (LVI; 46.97% vs. 23.08%; P = 0.001), coexisting intraductal papilloma (13.64% vs. 1.92%; P = 0.002), and ALN positivity (40.9% vs. 20.2%; P = 0.003). Sentinel lymph node positivity did not differ significantly between groups (21.2% vs. 24.0%; P = 0.669). In UFBC, T2 stage (adjusted odds ratio [OR]=4.437, 95% confidence interval [CI]: 1.410-13.965), LVI (OR = 5.064, 95% CI: 1.614-15.891), and invasive micropapillary carcinoma (OR = 6.580, 95% CI: 1.331-32.523) remained significantly associated with ALN metastasis. In MMBC, ordinal T stage and LVI were significant in univariate analyses but not after mutual adjustment. The optimism-corrected AUCs were 0.746 for the UFBC model and 0.664 for the MMBC model; the corresponding optimism-corrected Brier scores were 0.142 and 0.232.

In this exploratory retrospective study, MMBC was associated with higher frequencies of LVI, coexisting intraductal papilloma, and ALN positivity than UFBC. In UFBC, T stage, LVI, and IMPC remained significantly associated with ALN metastasis, whereas no factor remained statistically significant after mutual adjustment in MMBC. The UFBC model demonstrated moderate internally validated discrimination, whereas the MMBC model showed more limited performance. Given the small sample size, all findings and nomograms should be considered exploratory and require validation in larger independent cohorts.