Clinical and Translational Research
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Feb 24, 2022; 13(2): 135-146
Published online Feb 24, 2022. doi: 10.5306/wjco.v13.i2.135
Neurotrophic receptor tyrosine kinase family members in secretory and non-secretory breast carcinomas
Athina Stravodimou, Ioannis A Voutsadakis
Athina Stravodimou, Department of Medical Oncology, CHUV, Lausanne 1011, Switzerland
Ioannis A Voutsadakis, Department of Medical Oncology, Sault Area Hospital, Sault Ste Marie P6B0A8, Ontario, Canada
Author contributions: Both authors contributed to the conception of the study, literature review, data analysis, writing of the article and revising the article.
Institutional review board statement: No institutional review board approval was required or obtained as the study was not a clinical trial.
Clinical trial registration statement: This study was not registered as a clinical trial as it includes only data from publicly available previously published studies and no new patient information.
Informed consent statement: No informed consents have been obtained for this study as no new patients were included. The study analyzed publicly available data from previously published studies.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ioannis A Voutsadakis, MD, PhD, Associate Professor, Doctor, Department of Medical Oncology, Sault Area Hospital, 750 Great Northern Road, Sault Ste Marie P6B0A8, Ontario, Canada. ivoutsadakis@yahoo.com
Received: April 5, 2021
Peer-review started: April 5, 2021
First decision: July 6, 2021
Revised: July 11, 2021
Accepted: January 13, 2022
Article in press: January 13, 2022
Published online: February 24, 2022
Processing time: 323 Days and 15.7 Hours
Abstract
BACKGROUND

Breast cancer is the most common female cancer and a major cause of morbidity and mortality. Progress in breast cancer therapeutics has been attained with the introduction of targeted therapies for specific sub-sets. However, other subsets lack targeted interventions and thus there is persisting need for identification and characterization of molecular targets in order to advance breast cancer therapeutics.

AIM

To analyze the role of lesions in neurotrophic receptor tyrosine kinase (NTRK) genes in breast cancers.

METHODS

Analysis of publicly available genomic breast cancer datasets was performed for identification and characterization of cases with fusions and other molecular abnormalities involving NTRK1, NTRK2 and NTRK3 genes.

RESULTS

NTRK fusions are present in a small number of breast cancers at the extensive GENIE project data set which contains more than 10000 breast cancers. These cases are not identified as secretory in the database, suggesting that the histologic characterization is not always evident. In the breast cancer The Cancer Genome Atlas (TCGA) cohort the more common molecular lesion in NTRK genes is amplification of NTRK1 observed in 7.9% of breast cancers.

CONCLUSION

Neurotrophin receptors molecular lesions other than fusions are observed more often than fusions. However, currently available NTRK inhibitors are effective mainly for fusion lesions. Amplifications of NTRK1, being more frequent in breast cancers, could be a viable therapeutic target if inhibitors efficacious for them become available.

Keywords: Neurotrophic receptor tyrosine kinases; Breast cancer; Amplifications; Fusions; Tropomyosin related kinases

Core Tip: Molecular lesions in neurotrophic receptor tyrosine kinase (NTRK) receptors have been brought to the forefront of cancer therapy with the introduction of specific inhibitors which are effective in cancers with fusions involving the family of receptors. In breast cancer fusions involving the NTRK receptors are rarely seen and concern exclusively the secretory sub-type. In non-secretory breast carcinomas amplifications are observed in a minority of cases.