Simplified phenotyping of CYP2D6 for tamoxifen treatment using the N-desmethyl-tamoxifen/ endoxifen ratio
Clara Inkyung Lee,
Siew Kee Low,
Ricardo Maldonado,
Peter Fox,
Bavanthi Balakrishnar,
Sally Coulter,
Peter de Bruijn,
Stijn L.W. Koolen,
Bo Gao,
Jodi Lynch,
Nicholas Zdenkowski,
Rina Hui,
Christopher Liddle,
Ron H.J. Mathijssen,
Nicholas Wilcken,
Mark Wong,
Howard Gurney
Affiliations
Clara Inkyung Lee
Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia; Department of Medical Oncology, Bankstown-Lidcombe Hospital, Bankstown, Australia; Faculty of Medicine, University of New South Wales, Australia; Corresponding author. The University of Sydney and the University of New South Wales, Bankstown-Lidcombe Hospital, Bankstown, NSW, 2200, Australia.
Siew Kee Low
Sydney Medical School, University of Sydney, Camperdown, Australia
Ricardo Maldonado
Macquarie University, Australia
Peter Fox
Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia
Bavanthi Balakrishnar
Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia
Sally Coulter
Westmead Institute for Medical Research, Westmead, Australia
Peter de Bruijn
Erasmus University Medical Center, Rotterdam, the Netherlands
Stijn L.W. Koolen
Erasmus University Medical Center, Rotterdam, the Netherlands
Bo Gao
Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia
Jodi Lynch
St George Hospital, Kogarah, Australia; Sutherland Hospital, Caringbah, Australia
Nicholas Zdenkowski
Calvary Mater Hospital, Waratah, Australia
Rina Hui
Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia; Sydney Medical School, University of Sydney, Camperdown, Australia
Christopher Liddle
Sydney Medical School, University of Sydney, Camperdown, Australia; Westmead Institute for Medical Research, Westmead, Australia
Ron H.J. Mathijssen
Erasmus University Medical Center, Rotterdam, the Netherlands
Nicholas Wilcken
Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia; Sydney Medical School, University of Sydney, Camperdown, Australia
Mark Wong
Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia; Sydney Medical School, University of Sydney, Camperdown, Australia
Howard Gurney
Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia; Sydney Medical School, University of Sydney, Camperdown, Australia; Macquarie University, Australia
Introduction: CYP2D6 protein activity can be inferred from the ratio of N-desmethyl-tamoxifen (NDMT) to endoxifen (E). CYP2D6 polymorphisms are common and can affect CYP2D6 protein activity and E level. Some retrospective studies indicate that E 35; N = 44) groups. The ratio was independently validated by a validation cohort. The simplified system was better in predicting patients without slow metabolism, with specificity and sensitivity of 96% and 44% respectively, compared with the standard method - sensitivity 81% and specificity 83%. Conclusions: The simplified classification system based on whether any variant was present better identified patients who were truly not CYP2D6 slow metabolizers more accurately than the current system. However, as CYP2D6 genotype is not the only determinant of endoxifen level, we recommend that direct measurement of endoxifen should also be considered.
