Breast cancer is a heterogeneous disease. Most routine clinical care for breast cancer depends on conventional clinicopathologic prognostic factors (eg, TNM, stage, and comorbidity), prognostic or predictive biomarkers (eg, estrogen receptor [ER], progesterone receptor, human epidermal growth factor receptor 2 [HER2], and grade), and clinical guidelines (eg, St Gallen International Expert Consensus, National Cancer Comprehensive Network [NCCN], and National Cancer Institute). Breast cancers with similar clinicopathologic characteristics may have strikingly different outcomes. The “one size fits all” approach may prompt ineffective use of therapy, causing unnecessary toxic effects, delaying alternative treatments, and wasting economic resources. Gene expression profiling using DNA microarray measures the expression levels of large numbers of genes simultaneously to study the effects of certain treatments, diseases, and developmental stages on gene expression. A DNA microarray test could influence clinical care based on the individual molecular profile.1
A 70-gene MammaPrint signature (Agendia Inc, Huntington Beach, CA) measures 70 risk profile mRNAs and 536 quality and reference mRNAs to predict the likelihood of distant metastases for early-stage breast cancer (ESBC).2
It is the first assay to be cleared by the US Food and Drug Administration (FDA) using its new in vitro diagnostic multivariate index assay guidance.
A 70-gene signature was initially developed to predict the risk of developing distant metastases in 5 years for node-negative patients younger than 55 years.3
demonstrated the prognostic value of 70-gene signature independent of clinical risk classification. In a prospective multicenter study6
of 427 patients younger than 61 years, the use of 70-gene signature altered adjuvant treatment recommendations in 37% of patients, sparing 20% of patients from chemotherapy. In addition, 70-gene signature demonstrates clinical value in accurately selecting postmenopausal women for adjuvant chemotherapy and recently received FDA clearance for use among older women.7,8
Determining the extent to which 70-gene signature may influence clinical treatment decisions and ultimately outcomes may best be accomplished by prospective studies of prognosis and prediction of chemotherapy response; however, such studies take many years to complete.9
In awaiting that information, decision makers need to evaluate the economic and clinical trade-offs of the test, as well as factors that would influence its appropriate use.
Adjuvant! Online software (Adjuvant! Online
) (AS), a Web-based tool that calculates individualized 10-year survival probabilities and predicts benefit of adjuvant systemic therapy, is the most widely used prognostic tool to help inform clinicians and patients in decision making about therapeutic options. Risk estimates in AS were based on 10-year observed overall survival for women with ESBC in the Surveillance, Epidemiology and End Results (SEER) registry in the United States and were independently validated with the British Columbia Breast Cancer Outcomes Unit database and a large cohort of Dutch patient series.10,11
The objectives of our study were (1) to estimate the incremental benefits, costs, and cost-effectiveness of 70-gene signature– guided treatments vs AS-guided treatments using a decision analytic model, (2) to identify factors that contribute to the cost-effectiveness of 70-gene signature, and (3) to determine patient groups in which the use of 70-gene signature is optimal.
Figure 1. Risk Classification and Treatment Decision
AS indicates Adjuvant! Online software (Adjuvant! Online); ER, estrogen receptor; ESBC, early-stage breast cancer; and 70-gene signature, 70-gene MammaPrint signature (Agendia Inc, Huntington Beach, CA).
A decision analytic model from a US payer perspective was developed. Prognosis of a hypothetical cohort of women with ESBC was provided via 70-gene signature or AS to determine whether they were at high risk or low risk for distant metastases, on which the treatment was based. Because this evaluation critically depends on the quality of evidence related to the performance of 70-gene signature, the population assessed in this study was consistent with the FDA-cleared indication at the time of the analysis, namely, patients 60 years or younger with ER-independent, T1 or T2, lymph node– negative tumors. Because most US patients with HER2-positive tumors receive trastuzumabcontaining chemotherapy, these patients were excluded from our evaluation.