Non-secretory breast carcinomas lack NTRK rearrangements and TRK protein expression

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusions are actionable targets in various cancers.
• Secretory breast carcinomas are known to harbor NTRK rearrangements.
• Limited data exists on NTRK rearrangements and TRK protein expression in non-secretory breast carcinomas.

Purpose of the Study:

• To investigate the prevalence of TRK protein expression and NTRK gene rearrangements in a cohort of invasive breast carcinomas.
• To determine if non-secretory breast carcinomas harbor targetable NTRK alterations.

Main Methods:

• Utilized pan-TRK immunohistochemistry to detect TRK protein expression.
• Employed fluorescent in situ hybridization (FISH) to identify NTRK1, NTRK2, and NTRK3 gene rearrangements.
• Analyzed a tissue microarray of 339 invasive breast carcinomas.

Main Results:

• Only one case (1/339), a secretory breast carcinoma, showed positive pan-TRK expression and a confirmed NTRK1 rearrangement via FISH.
• No NTRK rearrangements or significant TRK protein expression were detected in the non-secretory breast carcinoma subtypes.
• This suggests NTRK alterations are exceedingly rare in non-secretory breast carcinomas.

Conclusions:

• Druggable NTRK rearrangements and associated TRK protein expression are not prevalent in non-secretory breast carcinomas.
• The findings underscore the importance of molecular profiling for identifying rare NTRK-rearranged secretory breast carcinomas.
• Current targeted therapies for NTRK rearrangements are unlikely to benefit patients with non-secretory breast carcinomas based on this data.