Due in large part to the investments made in biomedical research, advancements in treating, detecting, and preventing cancer
are evolving at a rapid rate. The wealth of information generated through research is being translated into new methods of selecting the right treatments for the right patients at the right time. This includes examining patients’ genetic characteristics that may impact health outcomes as a part of deciding the best treatment strategy. As the development and use of pharmacogenetic tests to predict response to treatment continues to increase, it is important to examine how such tests are being incorporated into the practice of oncology, as well as the clinically meaningful benefits of their use.
A recent technology assessment (Project ID Number: GEN0609 ) performed by the Agency for Healthcare Research & Quality (AHRQ) examined the published literature available for three different diseases that use pharmacogenetic tests:
§ Variations in CYP2D6 and response to tamoxifen in breast cancer,
§ Variations in KRAS and response to cetuximab and panitumumab in colorectal cancer
§ Variations in BCR-ABL1 and response to imatinib, dasatinib and nilotinib in chronic myeloid leukemia.
Each of these scenarios represents both the complexity and the promise associated with the use of pharmacogenetic tests. All are subject to robust, on-going clinical research. For this reason, we have concerns that considering this systematic literature review to make decisions to, or not to use these tests, independent of currently emerging scientific evidence, could be inaccurate and ultimately harmful to patients.
Regarding the impact of CYP2D6 polymorphisms on response to tamoxifen, this literature review may be in advance of the relevant information required for such an evaluation. [r1] Currently, multiple trials are underway or have been completed that will prospectively examine the role of CYP2D6 genotype on the clinical effect of tamoxifen treatment in both the metastatic and adjuvant setting. In addition, a study conducted by Schroth et. al., published after the timeframe of the technology assessment, retrospectively examined 1,325 patients treated with adjuvant tamoxifen for early stage breast cancer. The study concluded that, “Among women with breast cancer treated with tamoxifen, there was an association between CYP2D6 variation and clinical outcomes, such that the presence of two functional CYP2D6[r2] alleles was associated with better clinical outcomes and the presence of nonfunctional or reduced-function alleles with worse outcomes.”  While this study is not a randomized controlled trial, of which it may be several years until clinical results will demonstrate prospectively what the actual impact of altered drug metabolism is, the conclusions of this study are indicative of the complexity of the topic and weakness of the currently available evidence. Therefore, it would be difficult to conclude that pharmacogenetic testing for variations in CYP2D6 should not be used by physicians and patients with breast cancer to determine course of treatment.
 Schroth, W; Goetz, MP; et al. Association Between CYP2D6 Polymorphisms and Outcomes Among Women With Early Stage Breast Cancer Treated with Tamoxifen. JAMA. 2009; 302(13): 1429-36.