Abstract 131P
Background
NTRK1/2/3 kinase fusions are rare oncogenic drivers found in <1% of solid tumors. NTRK fusion-positive (NTRK+) solid tumors have shown meaningful clinical response to small molecule NTRK inhibitors such as entrectinib and larotrectinib, and broad genomic testing will help identify patients (pts) with these rare tumors. NTRK fusions occur more frequently in some cancers than others. For example, NTRK fusions are characteristic of secretory breast cancers (BCa), and it has been posited that non-secretory BCa lack druggable NTRK fusions. However, these conclusions were drawn on limited pt populations. Here we show evidence of NTRK fusions in both secretory and non-secretory breast tumors in the largest real-world cohort of NTRK+ breast tumors reported to date.
Methods
Comprehensive genomic profiling of up to 395 cancer-related genes, including NTRK1/2/3, was done at Foundation Medicine on de-identified all-comer BCa pts during the course of routine clinical care. Pathology reports and hematoxylin and eosin (H&E) images of NTRK+ breast tumors were examined by a pathologist for designation of secretory vs. non-secretory phenotype.
Results
NTRK fusions were identified in 21 BCa specimens. H&E images were available for review in 18 cases, and another was confirmed via the pathology report. Pathologist review of those 19 cases revealed that NTRK fusions were present in 14 with secretory phenotypes and 5 with non-secretory phenotypes. These cases stratified based on the specific NTRK fusion. Among the 14 secretory cases, 11 harbored an ETV6-NTRK3 fusion, 2 harbored a LMNA-NTRK1 fusion, and 1 harbored a TPM3-NTRK1 fusion. The 5 non-secretory cases harbored mostly NTRK1 fusions: TPM3-NTRK1 (2), MDM4-NTRK1 (1), GATAD2B-NTRK1 (1), and CDK12-NTRK3 (1).
Conclusions
While rare, NTRK fusions occur in a wide variety of tumor types. Within BCa, this includes both secretory and non-secretory phenotypes. These data are consistent with reported associations between secretory type BCa and the presence of NTRK fusions. However, we observed in our cohort that ∼1 in 4 NTRK fusions are found in tumors of the non-secretory subtype and tend to involve NTRK1. These data support NTRK fusion testing for pts with both secretory and non-secretory BCa subtypes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Genentech Inc.
Funding
Genentech Inc; Foundation Medicine.
Disclosure
T. Wilson: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment: Genentech Inc. E.S. Sokol: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment: Foundation Medicine Inc. J.S. Ross: Leadership role: Foundation Medicine; Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment: Foundation Medicine, Inc. S.L. Maund: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment: Genentech Inc.