Clinical Utility of Multigene Profiling Assays in Early-Stage Breast Cancer

Background: This clinical practice guideline was developed to determine the level of evidence supporting the clinical utility of commercially available multigene profiling assays and to provide guidance about whether certain breast cancer patient populations in Ontario would benefit from alternative tests in addition to Oncotype DX (Genomic Health, Redwood City, CA, U.S.A.). Methods: A systematic electronic Ovid search of the MEDLINE and EMBASE databases sought out systematic reviews and primary literature. A systematic review and practice guideline was written by a working group and was then reviewed and approved by Cancer Care Ontario’s Molecular Oncology Advisory Committee. Results: Twenty-four studies assessing the clinical utility of Oncotype DX, Prosigna (NanoString Technologies, Seattle, WA, U.S.A.), EndoPredict (Myriad Genetics, Salt Lake City, U.S.A.), and MammaPrint (Agendia, Irvine, CA, U.S.A.) were included in the evidence base. Conclusions: The clinical utility of multigene profiling assays is currently established for an appropriate subset of patients with estrogen receptor–positive, HER2-negative, node-negative breast cancer for whom a decision to give chemotherapy is difficult to make. For patients with estrogen receptor–positive tumours who receive tamoxifen alone, Oncotype DX, Prosigna, and EndoPredict validly identify a low-risk population with favourable outcomes, indicating that a low-risk assay result is actionable and the decision to withhold chemotherapy is supported. Clinical evidence indicates that a high Oncotype DX recurrence score can predict for chemotherapy benefit, but a high Prosigna or EndoPredict score, although prognostic, is not, based on clinical trial evidence, directly actionable. Prosigna and EndoPredict are statistically more likely to identify a population at risk for recurrence beyond 5 years, but that information is currently not actionable because of a lack of interventional studies.