Tumour profiling tests to guide adjuvant chemotherapy decisions in lymph node-positive early breast cancer: a systematic review and economic evaluation.

Background: Breast cancer is the most commonly diagnosed cancer in women in England. Breast cancer and chemotherapy treatment can impact upon patients' quality of life and survival. Tumour profiling tests can help to identify whether patients will benefit from chemotherapy. Objectives: To evaluate the effectiveness and cost-effectiveness of four tumour profiling tests (Oncotype DX, Prosigna, EPclin and MammaPrint), compared with current decision-making (no testing), to guide use of adjuvant chemotherapy in people with hormone-receptor positive, human epidermal growth factor receptor 2 negative, early-stage breast cancer with one to three positive lymph nodes. Methods and data sources: A systematic review identified studies via a literature search in April 2023 and from our previous review. The economic analysis included a review of existing models and development of an independent model. Results: Fifty-five articles were included, 42 for prognostic and predictive ability and 13 for impact on chemotherapy decisions. All four tests showed prognostic ability for determining risk of relapse. The RxPONDER randomised controlled trial of Oncotype DX indicated no chemotherapy benefit in post-menopausal lymph node-positive patients with a recurrence score of 0-25, but a statistically significant benefit in pre-menopausal patients with a recurrence score of 0-25. An older randomised controlled trial reanalysis (Southwest Oncology Group-8814) indicated lower relative chemotherapy benefit with lower recurrence score, with statistically significant interactions between recurrence score and chemotherapy benefit in some but not all analyses. There was no clear evidence of prediction of relative chemotherapy benefit for Prosigna, EPclin or MammaPrint. Decision impact studies in lymph node-positive populations in the United Kingdom and Europe were only available for Oncotype DX, and they reported a reduction of 12-75% in chemotherapy recommendations following testing. Based on the list prices of the tests and downstream treatments, the independent model suggests the following. Oncotype DX: This test dominates current decision-making in post-menopausal lymph node-positive women, provided an assumption of predictive benefit holds, but the test is dominated if this assumption does not hold. The test is dominated by current decision-making in pre-menopausal lymph node-positive women. Prosigna: The probabilistic incremental cost-effectiveness ratio for Prosigna versus current decision-making in post-menopausal lymph node-positive women is £39,357 per quality-adjusted life-year gained. EPclin: The probabilistic incremental cost-effectiveness ratio for EPclin versus current decision-making in post-menopausal lymph node-positive women is £4113 per quality-adjusted life-year gained. MammaPrint: Within clinical high-risk pre-/post-menopausal lymph node-positive women, MammaPrint is dominated by current decision-making. Limitations: There are limited data on the prediction of chemotherapy benefit; evidence for Oncotype DX may support a predictive benefit, but this is uncertain. Decision impact studies in a lymph node-positive population were available only for Oncotype DX. The economic model relies on an assumption of predictive benefit for Oncotype DX, and broader assumptions around the way that Prosigna, MammaPrint and EPclin test results would affect chemotherapy decisions. Conclusions: All four tests provide prognostic information on the risk of relapse. The evidence on prediction of relative chemotherapy benefit is weaker and mostly limited to Oncotype DX. The economic analyses indicate that Oncotype DX and EPclin may have favourable cost-effectiveness profiles in post-menopausal lymph node-positive subgroups, although this is uncertain. Study registration: This study is registered as PROSPERO CRD42023425638. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis Programme (NIHR award ref: NIHR135822) and is published in full in