Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers.

摘要: Abstract Introduction Spindle cell carcinoma is a rare subtype of metaplastic breast cancer, with triple-negative (TNBC: estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative) phenotype. It associated marked resistance to conventional chemotherapy and has an overall poor outcome. Materials Methods Twenty-three pure spindle carcinomas the (18 primary 5 recurrent/metastatic) were comprehensively explored for biomarkers immuno-oncology targeted therapies using immunohistochemistry DNA/RNA sequencing. Results The majority (21/23) TNBC. Estrogen androgen expression above therapeutic thresholds detected in 2 cases each. Pathogenic gene mutations identified 21 23 cases, including PIK3CA, TP53, HRAS, NF1, PTEN. One case matched pre- post-chemotherapy samples exhibited consistent mutational profile (PIK3CA HRAS mutations) both samples. Gene amplifications present 1 without detectable mutations. cohort had consistently low total burden (all below 80th percentile entire TNBC cohort). All tumors microsatellite stable. Programmed death-ligand was observed on tumor cells (in 7/21 cases), tumor-infiltrating immune (2/21 cases). Conclusions are characterized by targetable molecular alterations but owing lack uniform findings, individual patient profiling necessary. Detection combinations should improve treatment options this aggressive disease.