Subtype conversion and metastatic timing in breast cancer liver metastasis

Abstract

Breast cancer liver metastasis (BCLM) represents a critical stage of disease progression and is associated with poor survival outcomes. Molecular subtype discordance between primary tumors and metastatic lesions has been increasingly recognized; however, the relationships among subtype conversion, time to liver metastasis (TTLM), metastatic patterns, and survival outcomes remain insufficiently understood. Molecular subtypes of both primary tumors and liver metastases were classified as Luminal A, Luminal B, HER2+, or triple-negative breast cancer (TNBC). Logistic regression models were used to identify factors associated with subtype conversion and primary liver metastasis. Linear regression models were applied to explore factors related to TTLM. Overall survival (OS) was analyzed using Kaplan–Meier curves and Cox proportional hazards models. Among 205 patients with paired subtype information, the overall subtype conversion rate between primary tumors and liver metastases was 42.9%. Luminal A tumors demonstrated the highest conversion rate (79.7%), with Luminal A to Luminal B being the most frequent transition. Logistic regression analysis showed that longer TTLM was significantly associated with subtype conversion. In linear regression analysis, primary HER2 + subtype was consistently associated with a shorter TTLM. In survival analyses, larger liver metastatic lesions were independently associated with worse OS. The site of first metastasis was also an independent prognostic factor; compared with initial liver metastasis, initial bone metastasis was associated with significantly higher mortality risk. Patients with lung or brain metastases showed the worst survival outcomes. These findings highlight the importance of reassessing molecular subtype at the time of liver metastasis and integrating metastatic timing and dissemination patterns into risk stratification and individualized treatment strategies.