Oncotype DX-guided vs physician-directed chemotherapy and survival in HR+/HER2- breast cancer

Oncotype DX testing guides adjuvant chemotherapy decisions in early-stage hormone receptor-positive/HER2-negative breast cancer, but testing is not universally performed, and outcomes associated with genomic-informed versus clinicopathologic-based chemotherapy decision pathways remain unclear.

Using the 2022 National Cancer Database Breast Participant User File, we identified women diagnosed from 2010 to 2022 with pathologic T1b-T2, node-negative, hormone receptor-positive/HER2-negative invasive breast cancer who received adjuvant chemotherapy and endocrine therapy. Patients were classified into an Oncotype-guided group, defined by Oncotype DX testing with a recurrence score of 26 or higher, and a physician-directed group, defined by receipt of chemotherapy without genomic testing. The primary outcome was overall survival. Analyses used multivariable Cox models, logistic-IPTW and MLP-IPTW, restricted mean survival time analysis, and a Bayesian latent confounding survival model.

Among 56,625 women, 27,278 were in the Oncotype-guided group and 29,347 in the physician-directed group. Median ages were 59 and 56 years, respectively. The Oncotype-guided group had more favorable overall survival than the physician-directed group in multivariable Cox analysis (HR, 0.906; 95% CI, 0.856-0.959; P < 0.001), with similar findings in IPTW analyses. The association was concentrated among patients aged 56 years or older (HR, 0.866; 95% CI, 0.809-0.927; P < 0.001). The Bayesian model showed no strong residual confounding signal.

Among chemotherapy-treated women, an Oncotype-guided pathway was associated with more favorable overall survival than a physician-directed pathway, particularly among older patients, which indicating prognostic heterogeneity selected using genomic versus conventional clinicopathologic information.