BACKGROUND:  Approximately 60% of breast cancer cases are hormone sensitive. Tamoxifen is the most widely used treatment of hormone-dependent breast cancer. The pharmacological activity of tamoxifen is dependent on its conversion by the hepatic drug-metabolizing enzyme CYP2D6. Patients with reduced CYP2D6 activity may derive inferior therapeutic benefit from tamoxifen, and may alternatively be treated with newer aromatase inhibitors (AIs) sequentially or as monotherapy. However, the higher costs of AIs provide incentive for identifying patients who will benefit from tamoxifen prior to treatment. OBJECTIVES: To evaluate the cost-effectiveness of  adjuvant mono and sequential hormone therapies, and CYP2D6 testing in combination with tamoxifen mono and sequential (with AIs) therapies for ER+ hormone sensitive women with early breast cancer in Canada. METHODS:  We performed a cost-effectiveness analysis using a Markov model from a societal perspective with a lifetime horizon. An embedded decision tree was used to identify best treatment strategy according to CYP2D6 gene polymorphisms. Our comparator is optimal treatment strategy without genetic testing. Patient population is 65-year-old ER+ hormone sensitive women with early breast cancer. Expected value of perfect information was performed to identify future research directions. Probabilistic sensitivity analysis was used to incorporate parameter uncertainties. Outcomes were quality-adjusted life years (QALYs) and costs. RESULTS: Our preliminary analysis suggested that the genetic testing and treatment combination strategy were marginally more effective (0.005 QALY gained) and cost CAD $102 more when compared to no testing (letrozole-tamoxifen sequential therapy). The incremental cost-effectiveness ratio (ICER) for the base case was $21,732 per QALY. The results were sensitive to assumptions related to disease progression, mortality rate and the drug cost.  CONCLUSIONS: The marginal gain in effectiveness and extra cost may not warrant a recommendation for routine CYP2D6 genetic testing in combination with tamoxifen monotherapy for ER+ women with early breast cancer in the current setting.