NTRK, RET, ROS1, and ALK Gene Fusion in HER2 Immunohistochemistry 2+ Breast Carcinoma

Abstract ObjectiveHER2 immunohistochemistry (IHC) 2+ breast cancer patients need to determine the final HER2 status by fluorescence in situ hybridization (FISH) for selection of suitable treatment options. Although the HER2-positive cases can benefit from the anti-HER2 targeted therapy, it only made a small proportion of this group, so finding more targeted therapy methods is necessary. NTRK, RET, ROS1 and RET gene fusions have been fully investigated in non-small cell lung carcinoma and are subject to targeted therapy in clinical practice and trials. However, there are only few reports investigating these four fusion genes in breast cancer. Our study is designed to evaluate the four fusion genes in HER2 IHC 2+ breast cancer patients to find an alternative treatment option. MethodsOne hundred and seventy-seven tissue samples were included. IHC was employed to assess ALK and NTRK protein levels. FISH probes specific for HER2, ALK, NTRK1, NTRK2, NTRK3, ROS1 and RET were used. ResultsThe HER2-positivity rate of all HER2 IHC 2+ cases were 5.7%. The total fusion rate of the four oncogenes was 3.95% in HER2 IHC 2+ breast cancer patients. The fusion-positive patients were prone to be ER/PR/HER2 IHC triple negative (P=0.01) and were associated with poorly differentiated tumor (P=0.005). The NTRK, RET, ROS1, and ALK fusion rate was 0.56%, 1.13%, 1.13%, 1.13%, respectively. ConclusionsNRTK, RET, ROS1, and ALK fusion rearrangements were detected in triple-negative breast carcinoma patients which can provide patients with alternate treatment opportunities in clinical practice.