In 2011, an estimated 23,200 women in Canada will be diagnosed with breast cancer . Approximately half of them will be diagnosed with early-stage estrogen- or progesterone-receptor-positive, axillary lymph-node negative breast cancer (ER+/ PR + LN- ESBC) . Standard care for these patients usually includes local therapy (surgery with or without radiation) followed by adjuvant systematic therapy such as endocrine therapy alone (tamoxifen or aromatase inhibitors) or chemotherapy followed by endocrine therapy . Canadian guidelines specify that a patient’s risk of recurrence can be classified as low, intermediate or high and that adjuvant chemotherapy may be added when the benefits of treatment outweigh toxicities of therapy . However, evaluating the risks and benefits of chemotherapy based on the Canadian guidelines is difficult because the histopathologic measures that inform the guidelines are not accurate predictors of risk or benefits of chemotherapy [4–8]. A validated software program Adjuvant!Online (AOL) has been developed that projects outcomes at 10 years to assist oncologists in adjuvant decision-making process. However, AOL is also based on histopathologic measures.
The 21-gene recurrence score assay (Oncotype DX) produces a “tumour signature” reflecting tumour biology and risk of relapse [7, 9]. An algorithm produces a continuous variable known as the “recurrence score” (RS) reflecting prognosis, which ranges from 1 (lower risk) to 100 (higher risk), based on the expressions of the 21 genes isolated from tumour samples. Women with a score of less than 18 have a low risk of recurrence and typically have good outcomes from endocrine therapy alone , whereas those with a score of 31 or more have a high risk of recurrence and gain the largest expected benefit from the addition of chemotherapy to endocrine therapy. Women with a score between 18 and 30 have an intermediate risk and do not appear to have a large benefit from chemotherapy but the uncertainty in the estimate cannot exclude a clinically important benefit [9, 10].
The prognostic and predictive value of the RS-assay in women with ER+/PR + LN- ESBC was evaluated in retrospective analyses of the National Surgical Adjuvant Breast and Bowel Project (NSABP) chemotherapy-tamoxifen trials (B-14 and B-20) [7, 9, 11] in the United States. It was shown that among ER+/PR + LN- ESBC patients, approximately, 51% had a low RS, 22% a intermediate RS, and 27% a high RS [7, 9, 11]. The assay was found to be more accurate than histologic measures alone in predicting the likelihood of breast cancer recurrence (both loco-regional  and distant recurrence [7, 9]) and patient survival within 10 years of initial diagnosis , as well as benefit from adjuvant chemotherapy [9, 11]. Additionally, clinical significance of the RS-assay has been reported in the Asian population .
In 2007 the RS-assay was recommended in the National Comprehensive Cancer Network and American Society for Clinical Oncology guidelines as “evidence-based” to guide the use of adjuvant chemotherapy in all women with ER+/ PR + LN- ESBC [13, 14]. Public coverage of the 21-gene assay is limited and inconsistent across Canada. However, the use of the test with reimbursement mechanisms is likely increasing. It is available in Ontario through “out-of-country health services” which requires a request from an oncologist and pre-approval [15, 16]. In 2010 the Ontario Health Technology Advisory Committee (OHTAC) recommended that the assay be made available “within the context of a field evaluation” . It is also available in a limited fashion in British Columbia and Quebec . The test is not widely used and in 2010 less than 1000 patients received the test across Canada  but few field evaluations to establish its impact on Canadian practice are ongoing in British Colombia and Ontario.
According to the Annual Report Card of the Cancer Advocacy Coalition of Canada, the RS-assay will cost $4,000 CAD per patient including all Canadian system expenses . Previous cost-effectiveness analyses of the RS-assay in women with ER+/ PR + LN- ESBC in the US [18, 19], Japan [20, 21], Israel  and Canada [23, 24] suggested that it is likely to be cost saving or cost effective in this patient group. However, findings from studies in Israel  and Japan [19, 20] cannot be extrapolated to the Canadian context because of possible variations in clinical practice and different approaches to pricing and reimbursement. Additionally, analyses from the US [18, 19] and Canada [23, 24] did not use all relevant data and suffer from other limitations as indicated elsewhere .
Generation of recommendations for Canadian clinical practice guidelines regarding the use of RS-assay requires a comprehensive health economic evaluation of the assay in the Canadian setting. The purpose of this study was to conduct a cost-effectiveness analysis of the RS-assay versus current clinical practice (CCP) regarding adjuvant chemotherapy treatment in women with ER+/ PR + LN- ESBC from the perspective of the Canadian healthcare system.