Breast Cancer: Gene Mediating Tamoxifen Resistance Identified

Ben Ho Park, M.D., Ph.D. Associate Professor of Oncology, Breast Cancer Program Associate Director, Hematology/Oncology Fellowship Training Program The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD  21287MedicalResearch.com Interview with:
Ben Ho Park, M.D., Ph.D.
Associate Professor of Oncology, Breast Cancer Program
Associate Director, Hematology/Oncology Fellowship Training Program The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD  21287

Medical Research: What is the background for this study? What are the main findings?

Dr. Park: To discover genetic mediators of tamoxifen resistance in breast cancers, we used genetic screening of breast cancer cell line models and patient data to ​identify a new gene that can mediate drug resistance. We found that amplification and overexpression of this gene in estrogen receptor positive breast cancers results in tamoxifen resistance and is associated with worse outcomes in patients whose tumors demonstrate amplification/overexpression of this gene.

Medical Research: What should clinicians and patients take away from your report?

Dr. Park: This is still too early for use in clinical practice. It is mostly a laboratory based finding to identify the function of MACROD2 after we demonstrated that it is overexpressed/amplified in actual human breast cancers, and though future possibilities are compelling to think about, we need to proceed with additional high level evidence before we can use this information for clinical practice.​

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Park: We need to expand the study in a prospective fashion to confirm these results in patients. We also need to see whether existing and future drugs can overcome tamoxifen resistance mediated by MACROD2 in both the lab and clinical settings.​

Citation:

Morassa Mohseni, Justin Cidado, Sarah Croessmann, Karen Cravero, Ashley Cimino-Mathews, Hong Yuen Wong, Rob Scharpf, Daniel J. Zabransky, Abde M. Abukhdeir, Joseph P. Garay, Grace M. Wang, Julia A. Beaver, Rory L. Cochran, Brian G. Blair, D. Marc Rosen, Bracha Erlanger, Pedram Argani, Paula J. Hurley, Josh Lauring, Ben Ho Park. MACROD2overexpression mediates estrogen independent growth and tamoxifen resistance in breast cancers. Proceedings of the National Academy of Sciences, 2014; 201408650 DOI: 10.1073/pnas.1408650111