Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: Diagnostics guidance [DG34]

1 Recommendations
1.1 EndoPredict (EPclin score), Oncotype DX Breast Recurrence Score and Prosigna are recommended as options for guiding adjuvant chemotherapy decisions for people with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and lymph node (LN)-negative (including micrometastatic disease; see section 5.4) 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 (see section 5.29).
1.2 MammaPrint is not recommended for guiding adjuvant chemotherapy decisions for people with ER-positive, HER2-negative and LN-negative early breast cancer because it is not cost effective.
1.3 IHC4+C is not recommended for guiding adjuvant chemotherapy decisions for people with ER-positive, HER2-negative and LN-negative early breast cancer because the analytical validity of the test is uncertain.
Why the committee made these recommendations
People with early and locally advanced breast cancer may need further treatment (adjuvant treatment) after they have surgery. 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 people 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 people 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 people 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 people 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 the criteria in section 1.1 are met,
which includes collecting data on their use. Discussion about treatment options within the multidisciplinary team may be particularly helpful for people who have micrometastatic disease.
In people 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.

Author list includes the names of the NICE project team and Diagnostics advisory committee members -
NICE project team: Frances Nixon, Topic lead; Rebecca Albrow, Technical adviser; Donna Barnes,Project manager.
Diagnostics advisory committee; 22 standing committee members and additional specialist members. The committee members who participated in this assessment are named in the document and included in the author list for this record