Clinical Validation of the MammaTyper LRP Model for Identification of Low-Risk Patients With Early-Stage ER+/HER2- Breast Cancer: From Subtyping to Chemotherapy De-escalation.

BACKGROUND: Although Oncotype DX recurrence score (ODX-RS) has been proved its predictive and prognostic utility in ER+/HER2- BC, cost and accessibility limit its use. The MammaTyper BC subtyping assay derived LRP model has demonstrated to highly predict an ODX-RS ≤ 25. This study aimed to evaluate the prognostic value of the LRP model and its potential to identify patients who might forego CT. METHODS: In this retrospective study, women diagnosed with T1-2, N0-1, ER+/HER2- BC between 2014 and 2018 at Peking University First Hospital were included. Patients were stratified with the MammaTyper LRP model. Distant disease-free survival (DDFS) was compared using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Among 402 eligible patients, 221 (55%) were classified as low-risk by LRP. The 9-year DDFS rate was significantly higher in this group than in the high-risk group (96.2% vs. 87.0%; P = .0021). LRP low-risk status was an independent favourable prognostic factor for DDFS (adjusted Hazard ratio [HR] 0.37; P = .04). No significant DDFS differences were observed between endocrine therapy (ET) and ET + CT groups among LRP low-risk patients (HR 0.38; P > .05). Similarly, clinical risk-high/LRP-low patients did not benefit from CT in DDFS (HR 0.33; P > .05). CONCLUSION: The MammaTyper LRP model effectively identified a subset of low-risk patients with excellent long-term prognosis in 9-year DDFS from early BC. No significant DDFS benefits were observed from adjuvant CT in LRP low-risk patients, even in those with high-risk clinical features. These results support the LRP model identified low-risk patients might undergo CT de-escalation, warranting prospective validation.