Multigene testing to guide clinical adjuvant decisions in breast cancer: An overview focused on the assessment of the quality of evidence with the grading of recommendations assessment, development and evaluation (GRADE) approach.
Multigene tests have emerged as valuable tools in guiding adjuvant chemotherapy decisions for patients with ER-positive/HER2-negative early breast cancer. This study applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence supporting the clinical utility of these tests. We focused on OncotypeDX® and MammaPrint®, the two tests evaluated in prospective randomized trials. The analysis was structured around the clinical question of whether these tests should be recommended for patients with ER-positive, HER2-negative, lymph node-negative or up to 3 lymph nodes-positive invasive breast cancer to guide adjuvant chemotherapy decisions. Our findings reveal that OncotypeDX® demonstrates high clinical utility in sparing chemotherapy for older/postmenopausal patients, with convincing quality of evidence for both node-negative and node-positive patients. The clinical utility of MammaPrint® appears more controversial, with conflicting results between node-negative and node-positive patients. A particularly critical aspect remains the clinical usefulness of these tests in younger/premenopausal women, where the benefit of adjuvant chemotherapy was shown but with potential biases in the study designs. Despite the established role of multigene tests and their availability in Italy since 2021, their uptake in clinical practice remains suboptimal. This formal appraisal of the clinical utility of genomic tests, particularly OncotypeDX®, aims to reinforce their fundamental role in personalizing adjuvant treatment decisions and optimizing resource allocation. The study underscores the importance of these tests in sparing unnecessary chemotherapy toxicities and costs, while emphasizing the need for further research to address remaining uncertainties, especially in younger patient populations.