Genomic Risk Evaluation Using Oncotype DX in Young Women (Aged ≤40) With Early-stage, ER-positive, Human Epidermal Growth Factor Receptor 2-negative, and Node-negative Breast Cancer

Background: Multigene assays have become a key component in risk stratification of patients with HR+/human epidermal growth factor receptor 2-breast cancer. Among these, the Oncotype DX is a validated tool that predicts the risk of distant recurrence and the potential absolute benefit of adding chemotherapy to adjuvant endocrine therapy. Although breast cancer is less common in younger women, it is often associated with biologically more aggressive features and a worse prognosis. Moreover, this age group has been historically underrepresented in large, randomized clinical trials of Oncotype DX. Hence, younger women are less frequently evaluated with Oncotype DX, and even when testing is performed, the decision to administer chemotherapy is not always aligned with the recurrence score result. Methods: In this retrospective analysis, a total of 358 young patients were stratified into three genomic risk groups (low, intermediate, and high) according to their Oncotype DX Recurrence Score (RS). A subsequent subgroup analysis focused on identifying individuals within the low genomic risk category who were eligible for treatment with the cyclin-dependent kinase 4 and 6 inhibitor ribociclib. Results: Among the patients, 41% were classified as low genomic risk, 44% as intermediate, and 15% as high. Notably, 35% of the pT2 patients with low genomic risk were clinically high risk as per the NATALEE trial criteria. Conclusion: Despite the poorer prognosis in younger women, 41% had a low genomic risk and could potentially be treated effectively with endocrine therapy alone. Among those node-negative patients with tumor size 2–5 cm, one out of three (35%) were classified as clinically high-risk and could benefit from the addition of ribociclib.