Receptor Discordance and Molecular Subtype Changes in Visceral Metastases of Breast Cancer

Visceral metastases in breast cancer demonstrate considerable molecular heterogeneity. This study examines changes in receptor status and molecular subtypes between primary breast cancer and visceral metastases.

A retrospective analysis was conducted on 430 patients diagnosed with breast cancer and visceral metastases, including 138 with lung metastases and 292 with liver metastases. Receptor statuses (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2]) were assessed in both primary and metastatic tumors. Discordance in molecular subtypes was assessed, and factors influencing receptor changes were identified. Survival outcomes were estimated using Kaplan-Meier analysis.

Receptor discordance was observed in 47.9% (206/430) of patients, with a higher frequency in liver metastases (51.0%) than in lung metastases (41.3%). PR discordance was the most frequent (36.2%), followed by ER (18.9%) and HER2 (7.2%). Molecular subtype discordance occurred in 36.1% of patients, with the highest rate in Luminal A tumors (85.7%). Multivariate analysis identified pN3 stage and molecular subtype as independent predictors. Kaplan-Meier survival analysis showed that patients with ER gain had significantly improved disease-free survival (DFS) compared with those with ER loss (75.4 vs 44.5 months, P = 0.0092). Moreover, molecular subtype discordance was associated with longer DFS (63.9 vs 49.1 months, P = 0.0079).

This study emphasizes that there are significant differences in receptor expression and molecular subtypes between primary breast tumors and their visceral metastases. The receptor is more likely to change in patients with liver metastasis and Luminal A or Luminal B (HER2+) tumors, highlighting the importance of repeat biopsy in the metastatic environment. These findings can be used to identify high-risk patients and provide them with better treatment plans.