ABSTRACT

PURPOSE: Clinicopathological factors and the 21-gene Oncotype DX Breast Recurrence Score (RS) test both influence prognosis. Our goal was to develop a new tool, RSClinN1, to individualize recurrence risk and chemotherapy benefit predictions by menopausal status for patients with HR1/human epidermal growth factor receptor 2–negative, lymph node–positive breast cancer by integrating the RS result with clinicopathological factors (grade, tumor size, age).

METHODS: We used patient-level data from 5,283 patients treated with chemoendocrine therapy (CET) versus endocrine therapy alone (ET) in the S1007 (N 5 4,916) and S8814 (N 5 367) trials to develop the tool. Cox proportional hazards regression models stratified by trial were used to estimate 5-year invasive disease-free survival for pre- and postmenopausal woman, respectively. The integrated RSClinN1 model was compared with RS alone and clinicopathological models using likelihood ratio tests. Absolute CET benefit was estimated as the difference between ET and CET risk estimates. Validation of RSClinN1 was performed in 592 patients with node-positive disease in the Clalit Health Services registry.

RESULTS: RSClinN1 provides better prognostic information than RS model alone (premenopausal P 5 .034; postmenopausal P < .001) or clinicopathological model alone (premenopausal P 5 .002; postmenopausal, P < .001). In postmenopausal women, RS showed interaction with CET benefit (P 5 .016), with RSClinN1 absolute CET benefit ranging from <0.1% to 21.5% over RS ranges 0-50. In premenopausal patients with RS ≤25, there was no significant interaction between RS and CET benefit. In external validation, RSClinN1 risk estimates were prognostic (hazard ratio, 1.75 [95% CI, 1.38 to 2.20]) and concordant with observed risk (Lin’s concordance, 0.92).

CONCLUSION: RSClinN1 provides improved estimates of prognosis and absolute CET benefit for individual patients compared with RS or with clinical data alone and could be used in patient counseling.