Breast Cancer Liver Metastasis: Primary tumor predictors and histopathologic characteristics of metastatic lesions

Young breast cancer patients have increased risk for liver metastasis (BCLM), implicating age-dependent organotropism. To explore potential risk factors and mechanisms of BCLM, we unbiasedly recruited 47 patients diagnosed with BCLM at a tertiary medical center, collected clinicopathologic data of the primary breast cancers, and obtained paired BCLM lesion tissue. Compared to the overall breast cancer patient population, our BCLM cohort was enriched ~4 fold for young patients (YOBC) and ~5 fold for patients diagnosed within 10 years of recent childbirth. The majority of primary breast cancer diagnoses were luminal A, low-grade and early-stage disease, clinical attributes classically associated with good prognosis. Most BCLM lesions were also ER-positive, and the dominant breast cancer growth pattern was replacement. Immunohistology staining infers utilization of existing liver sinusoids, consistent with a passive mechanism of metastatic invasion. In sum, these data suggest that the liver readily supports metastatic establishment of early-stage, luminal A breast cancer cells. These data also support a growing body of literature linking postpartum liver biology to increased risk for BCLM, providing potential insight into the observed age-dependent organotropism of BCLM. Improved understanding of reproductive risk factors for BCLM may improve patient risk stratification and outcomes overall.