2 Clinical need and practice
2.1 The tumour profiling tests EndoPredict, MammaPrint, Oncotype DX Breast Recurrence Score, Prosigna and IHC4+C provide information on the activity of genes in tumour samples from people with early breast cancer. The results provide a risk profile of a person's breast cancer, which can be used with other routinely assessed clinical risk factors, such as nodal status and tumour size. It is claimed that the risk profile can be used to better predict the risk of disease recurrence. Some tests also claim to predict relative treatment effects for chemotherapy. This information is intended to help decision making about adjuvant chemotherapy use.
2.2 It is also claimed that people with early breast cancer identified as having a low risk of distant recurrence by a tumour profiling test may not need to have adjuvant chemotherapy. For these people, unnecessary treatment and therefore the comorbidities and negative effects on quality of life associated with chemotherapy could be avoided. Also, for people with early breast cancer at low risk of disease recurrence based on clinical and pathological features, the tests could confirm whether their risk is correct. If reclassified as being at high risk of recurrence, these people may benefit from chemotherapy. People with breast cancer and clinicians may also have more confidence that the treatment they are having or recommending is appropriate.
2.3 This assessment evaluates the clinical and cost effectiveness of EndoPredict, MammaPrint, Oncotype DX Breast Recurrence Score, Prosigna and IHC4+C when used to guide adjuvant chemotherapy decisions. The population was people with oestrogen receptor (ER)-positive (or progesterone receptor-positive or both), human epidermal growth factor receptor 2 (HER2)‑negative early breast cancer (stages 1 or 2) with 0 to 3 positive lymph nodes.
2.4 This is a full update of NICE's diagnostics guidance on gene expression profiling and expanded immunohistochemistry tests for guiding adjuvant chemotherapy decisions in early breast cancer management: MammaPrint, Oncotype DX, IHC4 and Mammostrat (DG10), which was published in 2013. This recommended Oncotype DX as an option for guiding adjuvant chemotherapy decisions for people with ER-positive, HER2-negative and lymph node-negative early breast cancer if the person was assessed as being at intermediate risk and the company provided Oncotype DX to NHS organisations according to the confidential arrangement agreed with NICE. The guidance also encouraged data collection on the use of Oncotype DX in the NHS, and further research on MammaPrint, IHC4 and Mammostrat. Since publication of the original guidance, Mammostrat is no longer available. Also, a new test, EndoPredict, has become available and PAM50 has been further developed into the Prosigna test.
2.5 Breast cancer is the most common cancer and the third most common cause of UK cancer-related deaths. One in 8 women and 1 in 870 men will be diagnosed with breast cancer during their lifetime (Cancer Research UK 2016). In 2014, 46,085 women and 332 men were newly diagnosed with breast cancer in England (Office for National Statistics 2016). Most breast cancer develops in women who are over the age of 50 (Cancer Research UK 2016).
2.6 Breast cancer survival depends on the stage of the disease at diagnosis, the treatment received and the biology of the tumour. More than 90% of women diagnosed with early breast cancer survive for at least 5 years, and 78% survive for 10 years (Cancer Research UK 2016). In contrast, only 13% of those diagnosed with advanced disease survive for more than 5 years.
2.7 Breast cancer may be diagnosed following an abnormal result in the NHS breast cancer screening programme, or after referral for further investigation because of signs or symptoms that could be associated with breast cancer. The referral criteria are described in NICE's guideline on suspected cancer.
2.8 When cancer cells have been detected in a biopsy sample, further tests are done to provide more information on the characteristics of the tumour. The results of these tests are used to categorise breast cancer into molecular subtypes and determine which types of treatment it is most likely to respond to. Recommendations on tumour testing are in NICE's guideline on early and locally advanced breast cancer. Tumour tests can include hormone receptor and HER2 tests. Although not routinely done, some laboratories may also test for Ki67, a marker of cell proliferation.
2.9 NICE's guideline on early and locally advanced breast cancer describes the care pathway. Surgery is often the initial treatment. Neoadjuvant treatment may be used before surgery, to reduce the size of the tumour and enable breast-conserving surgery.
2.10 After surgery, further treatment (adjuvant treatment) may be needed and this can include radiotherapy, chemotherapy, hormone therapy, biological therapy or a combination of these. The decision to offer adjuvant therapy, and the treatments to use, is made taking into account the clinical history, the stage and grade of disease, the likely course of the disease (prognosis), the molecular characteristics of the tumour and the person's preferences.
2.11 A variety of tools are available that can help to predict the likelihood of breast cancer recurrence based on clinical and pathological features. These may be used to provide prognostic information for patients and to guide the selection of adjuvant therapy. Expert advice suggests that the PREDICT tool version 2.0, an online prognostic and treatment benefit calculator, is the most widely used tool in the NHS in England to calculate risk of recurrence. Adjuvant! Online is not currently available online because it is being updated. It is not certain when it will be reinstated, and the website directs people to the PREDICT tool. Adjuvant! Online is described in the supplementary appendix of Cardoso et al. 2016. PREDICT is recommended in NICE's guideline on early and locally advanced breast cancer.