ABSTRACT
NTRK fusions represent a new biomarker-defined population that can be treated with TRK inhibitors. Although rare, NTRK fusions are detected across a wide range of solid tumors. Previous reports suggest that NTRK fusions are limited to the secretory subtype of breast cancer. Here we examined NTRK fusions in a large real world next-generation sequencing (NGS) dataset and confirmed secretory versus non-secretory status using H&E images. Of 23 NTRK fusion-positive cases, 11 were classified as secretory, 11 as non-secretory, and one as mixed status. The secretory subtype trended younger, was predominantly estrogen receptor (ER)-, had lower tumor mutational burden, and exhibited lower levels of genomic loss of heterozygosity. The non-secretory subtype was enriched for TP53 mutations. The secretory subtype was enriched for ETV6-NTRK3 fusions in 7 of 11 cases, and the non-secretory subtype had NTRK1 fusions in 7 of 11 cases, each with a different fusion partner. Our data suggests NTRK fusions are present in both secretory and non-secretory subtypes, and that comprehensive genomic profiling should be considered across all clinically advanced breast cancers to identify patients that could receive benefit from TRK inhibitors.
