Breast Cancer: CYP2D6 Remains Important Biomarker of Tamoxifen Effectiveness

Dr. Matthew P. Goetz, MD Associate Professor of Pncology Mayo ClinicMedicalResearch.com Interview with:
Dr. Matthew P. Goetz, MD
Associate Professor of Pncology
Mayo Clinic

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

Dr. Goetz: There has been conflicting data with regard to the importance of tamoxifen metabolism as measured by CYP2D6 genetic variation.   Two large “negative” studies were reported simultaneously in 2012 and these were referenced by guidelines that CYP2D6 should not be used to select hormonal therapy.   Our findings demonstrated that these studies were flawed in part based on analytical validity issues.  In short, the use of tumor tissue to derive CYP2D6 germline genotype leads to genotyping error in up to 45% of samples.

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

Dr. Goetz: Until prospective trials are available, guidelines regarding the use of CYP2D6 genotype should be derived from studies without evidence for genotyping error, and these studies show that CYP2D6 is an important marker of tamoxifen effectiveness.

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

Dr. Goetz: Analytical validity is obviously a key issue, and is a key issue for other biomarkers, especially when drugs or treatment recommendations are increasingly based on biomarkers.

Citation:

Loss of Heterozygosity at the CYP2D6 Locus in Breast Cancer: Implications for Germline Pharmacogenetic Studies
Matthew P. Goetz, James X. Sun, Vera J. Suman, Grace O. Silva, Charles M. Perou, Yusuke Nakamura, Nancy J. Cox, Philip J. Stephens, Vincent A. Miller, Jeffrey S. Ross,

David Chen, Stephanie L. Safgren, Mary J. Kuffel, Matthew M. Ames, Krishna R. Kalari, Henry L. Gomez, Ana M. Gonzalez-Angulo, Octavio Burgues,

JNCI J Natl Cancer Inst (2015) 107 (2): dju401 doi:10.1093/jnci/dju401