Differences in Biomarkers between the Primary Tumor and Axillary Lymph Nodes in Invasive Lobular Carcinoma: A Retrospective Study

Introduction: Invasive lobular carcinoma (ILC) is a distinct histological subtype of breast cancer characterized by hormone receptor positivity, low proliferative activity, and unique metastatic patterns. However, recent evidence suggests that biomarker profiles in metastatic sites may differ from those in primary tumors, potentially reflecting biological heterogeneity. Methods: A retrospective review was conducted on 108 patients diagnosed with ILC who underwent immunohistochemical evaluation of both primary breast tumor and metastatic axillary lymph node specimens between 2012 and 2021. Differences in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 expression were analyzed using paired statistical tests, including McNemar’s and Wilcoxon signed-rank tests. Subgroup analyses were performed according to the receipt of neoadjuvant chemotherapy (NeoCT), although findings in the NeoCT subgroup were interpreted as exploratory because treatment may influence biomarker expression. Histological grade was also evaluated, and its association with primary tumor Ki-67 was analyzed exploratorily. Results: No significant differences were observed in ER, PR, or HER2 expression between primary tumors and metastatic axillary lymph nodes (p > 0.05). However, a significant increase in the Ki-67 proliferation index was found in metastatic lymph nodes compared with matched primary tumors (median 28% vs. 18%, p < 0.001). Consequently, 37.9% of patients exhibited a surrogate molecular subtype conversion from Luminal A-like to Luminal B-like. Histological grade was significantly associated with primary tumor Ki-67, with median values of 10%, 12.5%, and 32.5% for grade 1, grade 2, and grade 3 tumors, respectively (p = 0.00014). Conclusion: Metastatic axillary lymph nodes in ILC display higher proliferative activity compared to primary tumors, resulting in a substantial rate of conversion from Luminal A-like to Luminal B-like. These findings support biological heterogeneity between primary and nodal disease; however, their direct prognostic and therapeutic implications remain uncertain.