NICE Issues Diagnostics Guidance on Tumour Profiling Tests to Guide Adjuvant Chemotherapy Decisions in Early Breast Cancer

EndoPredict, Oncotype DX Breast Recurrence Score and Prosigna are recommended, while MammaPrint and IHC4+C are not

In December 2018, the NICE has released a diagnostic guidance on tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer. Evidence-based recommendations concern theEndoPredict (EPclin score), Oncotype DX Breast Recurrence Score, Prosigna, MammaPrint and IHC4+C tests. The EndoPredict (EPclin score), Oncotype DX Breast Recurrence Score and Prosigna are recommended as options for guiding adjuvant chemotherapy decisions for patients with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and lymph node (LN)-negative (including micrometastatic disease) early breast cancer, only if:

  • they have an intermediate risk of distant recurrence using a validated tool such as PREDICT or the Nottingham Prognostic Index
  • information provided by the test would help them choose, with their clinician, whether or not to have adjuvant chemotherapy taking into account their preference
  • the companies provide the tests to the NHS with the discounts agreed in the access proposals and
  • clinicians and companies make timely, complete and linkable record-level test data available to the National Cancer Registration and Analysis Service as described in the data collection arrangements agreed with NICE. 

MammaPrint is not recommended for guiding adjuvant chemotherapy decisions for patients with ER-positive, HER2‑negative and LN-negative early breast cancer because it is not cost effective.

IHC4+C is not recommended for guiding adjuvant chemotherapy decisions for patients with ER-positive, HER2-negative and LN‑negative early breast cancer because the analytical validity of the test is uncertain. 

Why the appraisal committee made these recommendations? 

Tools such as PREDICT, which is used by many NHS trusts, provide prognostic information to help guide the selection of adjuvant treatment. Additional information from tumour profiling tests may be helpful for patients whose cancer has an intermediate risk of distant recurrence when the decision to offer chemotherapy is unclear.

Evidence suggests that EndoPredict (EPclin score), Oncotype DX Breast Recurrence Score, MammaPrint and Prosigna can predict the risk of distant recurrence in patients who have ER-positive, HER2-negative, early breast cancer. This evidence is strongest in the group with LN-negative disease, which is likely to include patients with micrometastatic disease. Also, Oncotype DX Breast Recurrence Score may be able to predict who will respond to chemotherapy, but the evidence for this is uncertain.

There are uncertainties in the economic modelling, particularly around the pre- and post-test chemotherapy decisions and the effect of adjuvant chemotherapy on distant recurrence. Also, there are no data available to compare the tumour profiling tests with PREDICT, or to define the clinical risk groups using PREDICT. 

Using the access proposal test costs for EndoPredict (EPclin score), Oncotype DX Breast Recurrence Score and Prosigna, all 3 tests would provide value for money in patients with LN-negative disease and an intermediate risk of distant recurrence. But because of the uncertainty about their effects on clinical decision making and clinical outcomes, the tests are recommended as options for guiding adjuvant chemotherapy decisions only if above mentioned criteria are met, which includes collecting data on their use. Discussion about treatment options within the multidisciplinary team may be particularly helpful for patients who have micrometastatic disease. 

In patients with an intermediate to high risk of distant recurrence, MammaPrint is less clinically effective and costs more than current practice, which does not use tumour profiling tests. It is therefore not recommended for use in the NHS.

IHC4+C appears to be cost effective, but there are concerns about its analytical validity, for example the reproducibility of test results. It is therefore not recommended for use in the NHS.

Genomic Health, Myriad Genetics and NanoString Technologies have all offered their tumour profiling tests to the NHS under access proposals that make each test available to the NHS at a revised price. The proposal prices are commercial in confidence. It is the responsibility of the companies to communicate details of their proposal to the relevant NHS organisations.