Breast cancer is the most commonly diagnosed cancer in women in Ireland. The majority of newly diagnosed cases are hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), early-stage (stage I-IIIa) breast cancer. Surgery is considered the first-line treatment for these patients. Following surgery, further therapy, including chemotherapy, may be needed. Chemotherapy can reduce the risk of recurrence and has contributed to declining breast cancer mortality; however, some patients may not benefit from chemotherapy and so could be spared its side effects and complications. GEP tests have been developed to inform decisions regarding the use of chemotherapy in breast cancer. GEP tests are intended to provide information on disease prognosis and some may also be able to identify the patients who are most likely to benefit from chemotherapy. In this way they support clinical decision-making regarding a patient’s need for adjuvant chemotherapy. Currently in Ireland, the HSE reimburses the Oncotype DX® GEP test. However, there are three other GEP tests available that are not reimbursed by the HSE: MammaPrint®, EndoPredict®, and Prosigna®.

• The Terms of Reference of the rapid HTA were agreed between HIQA and the HSE NCCP.
• A multidisciplinary expert advisory group (EAG) was convened by HIQA comprising representation from relevant stakeholders. These included the HSE NCCP, clinicians with specialist expertise in medical oncology, breast cancer surgery and histopathology, representation from people affected by cancer, as well as representation from the Irish Cancer Society research department.  
• A protocol for the systematic review of clinical effectiveness was agreed with the HSE NCCP and reviewed by the EAG. 
• The clinical pathway for the screening, diagnosis and treatment of breast cancer in Ireland was described.
• The technical characteristics of the GEP tests, and international practice in relation to the use of GEP tests was described.
• The burden of disease associated with early breast cancer in Ireland was described. 
• A systematic review was undertaken to review the clinical effectiveness of GEP tests.
• The draft report was reviewed by the Expert Advisory Group. A final draft report was submitted to the Board of HIQA for approval. Following its approval, the completed assessment was submitted to the HSE NCCP as advice.
   

HIQA’s advice to the Health Service Executive National Cancer Control Programme arising from this rapid HTA is as follows:

In Ireland, on average approximately 1,800 cases of HR+, HER2- stage I-IIIa breast cancer were diagnosed each year between 2015 and 2019. The majority of these patients receive Oncotype DX® testing.

Oncotype DX® is a gene expression profiling (GEP) test that is used to provide information on disease prognosis and to predict the potential for benefit from adjuvant chemotherapy. This information supports clinical decision-making regarding the need for adjuvant chemotherapy.

There are three other commercially available GEP tests (MammaPrint®, EndoPredict®, and Prosigna®), two of which are indicated for predictive use (MammaPrint® and EndoPredict®). Currently, these three tests are not reimbursed by the HSE.

To provide advice to the HSE on these alternative tests, a review of the clinical effectiveness evidence was undertaken. Taking into account the notable limitations of the evidence,.

Among LN- patients:

• All four commercially available tests examined in the HTA provide prognostic information.
• Considering predictive ability, although there are limited data to differentiate between the tests, the available evidence supports the continued use of Oncotype DX®.

Among LN+ patients:

• All four commercially available tests examined in the HTA were found to provide prognostic information.
• Considering predictive ability, the evidence most strongly supports the continued use of Oncotype DX® in postmenopausal women, based on available five-year follow-up data.

A decision to reimburse GEP tests other than Oncotype DX® should take account of differences in factors such as test indications, test costs and feasibility of use, particularly with respect to laboratory resources.

In order to optimise the management and use of GEP tests in Ireland, consideration should be given to:

• collecting data on GEP test use, linked to treatment and patient characteristics and outcomes, as part of a national database. These data could help clarify the clinical impact of these tests in Ireland.
• developing guidance to outline the patient subgroups in which they should be used, the appropriate tumour sampling methods and preparation techniques, and interpretation of test results.