Title: Tumour profiling tests to guide adjuvant chemotherapy decisions in people with breast cancer
Funder: Department of Health and Social Care

Abstract: Do tumour profiling tests used for guiding adjuvant chemotherapy decision in patients with early stage breast cancer represent a clinical- and cost-effective use of NHS resources? This project will update the systematic review and cost-effectiveness analysis3 that informed Nice Diagnostics Guidance 10 (DG104).

Lay abstract: Breast cancer is the most commonly diagnosed cancer and the third most common cause of cancer related deaths in the UK. In 2014, 46,085 women and 332 men were diagnosed with breast cancer in England, while 11,360 women and 73 men died from breast cancer in the UK. Treatment usually involves surgery to remove the tumour and any involved lymph nodes. This may be followed by one or more of the following: radiotherapy, endocrine (hormone) therapy, trastuzumab and/or chemotherapy. There are various prognostic tools that help patients and clinicians make treatment decisions by predicting the risk of the disease coming back (recurring) after surgery. These include the Nottingham Prognostic Index (NPI), PREDICT and Adjuvant! Online. They predict the risk of recurrence, based on pathological information (e.g. tumour size, grade and lymph node status for NPI), plus other factors including oestrogen receptor (ER) status, age and co-morbidity for Adjuvant! Online and PREDICT. However, it has been suggested that these clinical tools do not predict recurrence and response to treatment particularly well for some patients (Paik, 20071). This presents a challenge to clinicians in making decisions relating to whether or not to recommend the use adjuvant chemotherapy (chemotherapy after surgery) in people with early stage breast cancer (Stages I, II (A or B) and IIIA2). Tumour profiling, using either gene expression profiling or protein expression profiling (with immunohistochemistry), seeks to identify genes or proteins that may be helpful in assessing disease prognosis and guiding therapy. Improved information on a patient’s risk of recurrence (i.e. prognostic risk) and/or likely response to chemotherapy (i.e. predictive benefit) may help target chemotherapy at those patients who will benefit the most. Avoiding chemotherapy in patients at low risk of recurrence, and who would therefore obtain limited benefit, avoids the unpleasant side effects of chemotherapy and reduces expenditure on both the chemotherapy itself and the treatment of these side effects. It is therefore important to understand the benefits offered by these tumour profiling tests compared with existing prognostic tools and whether or not they represent a good use of National Health Service (NHS) resources. A previous systematic review and economic evaluation, published in 2013, considered the clinical effectiveness and cost-effectiveness of tumour profiling tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in women with early breast cancer in England and Wales. This report informed the NICE decision to approve the use of Oncotype DX as an option for guiding adjuvant chemotherapy decisions for people with ER positive, lymph node negative and human epidermal growth factor receptor 2 (HER2) negative early breast cancer assessed to be at intermediate risk of recurrence of breast cancer after surgery. This review aims to update the previous report by systematically evaluating the most recent evidence on the use of five tumour profiling tests to guide adjuvant chemotherapy treatment decisions in early breast cancer management, and by conducting an economic evaluation to determine if these tests represent good value for money to the NHS.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS