Association of DNA Copy Number Aberrations with Organ-Specific Metastasis in Luminal B HER2-Negative Breast Cancer

Breast cancer (BC) exhibits considerable metastatic heterogeneity and distinct patterns of organotropism, which contribute to differences in patient outcomes and therapeutic responses. However, the molecular mechanisms underlying this organ specificity remain incompletely understood. Objective: To investigate the genetic landscape of primary breast tumor, surgical specimens, and metastatic lesions and to identify copy number aberration (CNA) regions associated with organ-specific metastatic-site patterns in breast cancer. Materials and methods: The study included paired pretreatment and post-treatment surgical specimens from 50 patients with BC (T1–4N0–3M0) and hematogenous metastases. In addition, three samples (biopsy, surgical specimen, and metastatic lesion) were obtained from four patients with primary metastatic BC (with metastasis to the bones, lungs, liver, and brain). Microarray analysis was performed using high-density CytoScanTM HD Array DNA chips (Affymetrix (USA)). Results: The following CNA regions were associated with organ-specific metastatic-site patterns: bone metastasis was associated with a higher frequency of amplifications in the 14q32.33 region (p = 0.0144); liver metastasis was associated with a higher frequency of amplifications in the 17q23.2 region (p = 0.0042, confirmed by validation on an independent cohort); lung metastasis was associated with a higher frequency of deletions in the 2p13.1 and 19p13.12 regions (p = 0.0449); and brain metastasis was associated with a higher frequency of deletions in the 19q12 region (p = 0.0522) and in the 20q11.22 region (p = 0.0089, confirmed by validation in an independent cohort). Conclusions: Our findings identify CNA regions associated with organ-specific metastatic-site patterns in breast cancer patients.