Impact of Metabolizing Enzymes on Drug Response of Endocrine Therapy in Breast Cancer

Pilar H Saladores; Jana C Precht; Werner Schroth; Hiltrud Brauch; Matthias Schwab


Expert Rev Mol Diagn. 2013;13(4):349-65. 

In This Article

Five-Year View

The controversy surrounding the clinical validity of CYP2D6 genetic testing in tamoxifen therapy will most likely not abate in the near future. However, as it stands, the current evidence suggest that CYP2D6 matters and CYP2D6 genetics may provide useful information to support the choice of endocrine treatment for postmenopausal breast cancer patients, in that CYP2D6 PM patients may benefit more from AI therapy, which is a valid treatment option to tamoxifen. Whether implemented in routine testing or not, the challenge in this is to conduct the genetic testing at the highest standards to avoid confounders. Future research should address those factors that influence CYP2D6 phenotype prediction and this will include other metabolizing enzymes for their contribution to tamoxifen efficacy. Current results of the ATLAS trial could influence tamoxifen therapy recommendations in prolonging duration of treatment up to 10 years. Therefore, predicting the drug's efficacy before the start of a long-term treatment will be of greater importance to aid both the patients and the healthcare system. Regarding AIs, future research will contribute to the understanding of a possible role of DMEs in therapy outcome.