OBJECTIVES : Adjuvant chemo-endocrine therapy is used to reduce the risk of recurrence in HR+, HER2– early breast cancer. Not all patients benefit equally from chemotherapy and inappropriate chemotherapy use is associated with short and long-term adverse events. Despite efforts for a pan-European HTA process to assess the evidence level of gene expression tests, countries still use national assessments and reimbursement procedures. A comparative analysis of the assessment and reimbursement of gene expression tests was performed.

METHODS : Inclusion criteria were publicly available HTA decisions and reimbursement status in preselected European countries for gene expression tests. The following HTA reports were analyzed: Austria, Belgium, France, The Netherlands, Switzerland, England, Scotland, and EUnetHTA. Four tests were evaluated: Oncotype DX^® test, MammaPrint^®, EndoPredict^® and Prosigna^®.

RESULTS : All assessments were published between 2014 – 2020. Oncotype DX test was assessed in 5 countries, MammaPrint in 6 countries, EndoPredict and Prosigna in 4 countries. France (2019), Belgium (2015), England (2018), and Germany (2020) assessed all tests at the same time. The Netherlands and EUnetHTA (2018) assessed only MammaPrint. Austria (2014) assessed Oncotype DX test only.

Three reimbursement approaches can be differentiated: 1. Reimbursed tests - Germany (only Oncotype DX test) and England (Oncotype DX test, EndoPredict and Prosigna). 2. Innovation funding with data collection - France (all tests), Belgium (Oncotype DX test and MammaPrint) and Switzerland (all tests). 3. Rejected tests - Netherlands rejected MammaPrint reimbursement.

CONCLUSIONS : HTA assessments varied in selection of tests assessed, timeframe and led to different reimbursement status across Europe. To date the Oncotype DX test is the only test with long-term prospective RCT data confirming chemotherapy benefit prediction with precision but this didn’t lead to harmonization of HTA assessment conclusions.