Authors' objectives: 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. 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. Breast cancer is the most commonly diagnosed cancer in women and the fourth most common cause of cancer-related death in the UK. Most people with lymph node-positive (LN+) breast cancer receive adjuvant chemotherapy due to their increased risk of recurrence. However, chemotherapy is associated with considerable adverse effects. Currently, adjuvant chemotherapy decisions may be informed by clinical and pathological information, sometimes via a risk prediction tool. Improved information on a patient’s risk of recurrence (i.e. their prognostic risk) and/or their likely response to chemotherapy (i.e. predictive benefit) may help clinicians to target chemotherapy to patients who will benefit most. Tumour profiling tests aim to improve decisions on chemotherapy use by improving the categorisation of patients according to risk and the identification of patients who will benefit most from chemotherapy. In 2018, the National Institute for Health and Care Excellence (NICE) published Diagnostics Guidance (DG) No. 34. DG34 recommends the use of Oncotype DX, Prosigna and EndoPredict (EPclin) for guiding chemotherapy decisions in people with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2) negative, lymph node-negative (LN0) early breast cancer, including those with micrometastases. Two other tests assessed in DG34 (MammaPrint and immunohistochemical 4 (IHC4)) were not recommended in the LN0 population. While DG34 also assessed these tests in women with LN+ early breast cancer, the Appraisal Committee did not make any specific recommendations on the use of any test within LN+ patients. This assessment provides an updated systematic literature review and economic analysis of four tumour profiling tests (Oncotype DX, Prosigna, EPclin and MammaPrint) compared to current decision-making in women with ER-positive [and/or progesterone receptor (PR)-positive], HER2-negative, early breast cancer with one to three positive lymph nodes. The main research question is: ‘Do tumour profiling tests used for guiding adjuvant chemotherapy decisions in patients with ER-positive (and/or PR-positive), HER2-negative, early-stage breast cancer with 1 to 3 positive lymph nodes represent a clinically effective and cost-effective use of NHS resources?’ The objectives are: To conduct a systematic review of effectiveness and cost-effectiveness of four tumour profiling tests (Oncotype DX, Prosigna, EPclin and MammaPrint). To develop a health economic model to assess the cost-effectiveness of tumour profiling tests compared with current decision-making (no testing) on the use of chemotherapy from the perspective of the NHS and Personal Social Services (PSS).

Authors' results and conclusions: 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: 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. Clinical evidence results Overview of available evidence In total, 55 articles were included, 42 relating to prognostic and predictive ability, and 13 relating to impact on chemotherapy decisions. Data were reported for two prospective RCTs (RxPONDER and MINDACT). In RxPONDER, LN+ patients with an Oncotype DX Breast Recurrence Score (RS) of 0–25 were randomised to chemotherapy versus no chemotherapy. In MINDACT, patients with discordant MammaPrint risk and clinical risk were randomised to chemotherapy versus no chemotherapy. In addition, the ongoing OPTIMA RCT compares Prosigna test-directed chemotherapy use versus standard chemotherapy use; however, results are not yet available.

Authors' methods: 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. 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. Clinical evidence review methods The External Assessment Group (EAG) undertook a systematic review of Oncotype DX, Prosigna, EPclin and MammaPrint for guiding adjuvant chemotherapy decisions in women with ER+/PR+, HER2− early breast cancer where the study population was at least 80% LN+. Studies were identified from the previous review which informed NICE DG34 (searches conducted in 2017) plus an updated search (April 2023) covering MEDLINE, EMBASE, Cochrane, and other sources. Eligible data types included prospective randomised controlled trials (RCTs) and studies of prognostic ability, prediction of relative chemotherapy benefit, impact of tests on chemotherapy decisions (restricted to UK and European studies), and health-related quality of life (HRQoL) and anxiety associated with testing.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR135822

Year Published: 2025

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/KGFD4040

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/KGFD4040

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk