2023 update: clinical utility of genomic signatures in early-stage HR-positive/HER2-negative breast cancer - InaHTA Brief

In 2019, the French National Authority for Health (HAS) evaluated the clinical utility of four genomic signatures (Oncotype Dx, Mammaprint, Prosigna, Endopredict) in early-stage hormone-receptor-positive (HR+) breast cancer with HER2-negative status (HER2-). Genomic signatures could be used as a guide to safely de-escalate adjuvant chemotherapy (ACT) in certain patient profiles in situations of clear decision-making uncertainty, with a low or favourable genomic score enabling the avoidance of unnecessary decisions to administer ACT. Based on the data available and the consultations carried out at the time, the HAS had returned an unfavourable opinion for coverage of testing for these four genomic signatures. But it issued a favourable opinion for temporary funding as part of a specific funding program for research and innovation (RIHN) to maintain access to these innovative tests in a potential population of interest. In 2021 and 2022, the publication of new intermediate data led to changes being made to several international guidelines, reporting a risk of loss of chance in terms of oncological outcome in some premenopausal patients aged 50 or under linked to genomic signatures. At the end of 2022, in view of this risk of loss of chance in terms of oncological outcome, the HAS decided to update its assessment of the four genomic signatures and to redefine the scope of the eligible target population to guarantee the oncological safety of patients and limit the risk of misuse by healthcare professionals.