Abstract P1-11-02: Risk of Recurrence by Nodal Status and High-Risk Features in Patients with HR+, HER2-, Early Breast Cancer: An Analysis of Real-world Data

Abstract Background: Tumor involvement of axillary lymph nodes (ALN) is the most significant prognostic marker for recurrence for HR+, HER2- early breast cancer (EBC). For node-positive EBC, most patients (76%) present with 1-3 ALN (N1) disease; however, outcomes for N1 disease are variable. The monarchE trial selected patients at high risk of recurrence based on nodal status and included patients with 4-9 ALN (N2) or ≥10 ALN (N3); however, patients with N1 disease were required to have additional clinicopathological risk features including tumor size ≥5 cm and/or grade 3 disease. To further evaluate the risk of recurrence in patients with N1 disease, real-world data were used to describe outcomes for patients with N1 disease with and without high-risk clinicopathological features. Outcomes for patients with node-negative (N0) disease and N2 and N3 disease were also described for additional context. Methods: This study used the US nationwide Flatiron Health electronic health record (EHR)-derived de-identified database, predominantly with patients from community oncology settings. The database included >15,000 patients diagnosed with EBC from Jan 2011. Data cut-off was September 2020. Eligible patients had: (1) pathological stage I-III, HR+, HER2- disease, (2) undergone definitive surgery for primary breast tumor, and (3) initiated adjuvant ET by March 2020. Patients with N1 disease and high-risk clinicopathological features (i.e., tumor size ≥5 cm and/or grade 3) were assigned to the high-risk group (N1-HRG) and patients with N1 disease who did not meet monarchE criteria were assigned to the non-high-risk group (N1-NHRG). IDFS was defined as time from adjuvant ET initiation to recurrence or death; patients without events were censored at last structured EHR activity date prior to data cut-off. IDFS was estimated using the Kaplan-Meier (KM) method. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for N1-HRG vs N1-NHRG (and vs N0), adjusting for patient and disease characteristics. Additional models evaluated N2, N3, and N1-HRG+N2+N3 each vs patients who did not meet monarchE criteria (NHRG). Patient and disease characteristics were summarized descriptively for all (sub)groups. Results: 4658 patients met eligibility criteria, with N1-HRG (n=286), N2 (n=161), N3 (n=99), and NHRG (n=3999; N1-NHRG [n=548], N0 [n=3293]). Median follow-up was 43.5 months for N1-HRG+N2+N3 and 42.2 months for NHRG. For N1-HRG, 67% of patients had stage II, 82% had grade 3, and 25% had tumor size ≥5 cm. Five-year IDFS rates were 74% for N1-HRG, 89% for N1-NHRG, and 93% for N0. Recurrence risk for N1-HRG was >2-fold as high as N1-NHRG and N0 with adjusted HR (95% CI) of 2.18 (1.45, 3.29; nominal p-value = 0.0002) and 2.97 (2.19, 4.02; nominal p-value <0.0001), respectively. Five-year IDFS rates were 66% for N2, 65% for N3, and 71% for N1-HRG+N2+N3. Relative to NHRG, HR (95% CI) was 3.68 (2.63, 5.15) for N2, 4.03 (2.75, 5.91) for N3, and 3.25 (2.62, 4.03) for N1-HRG+N2+N3. Additional characteristics and KM curves for (sub)groups will be presented. Conclusion: These real-world data demonstrate that patients with N1 EBC and high-risk clinicopathological features had a recurrence risk of 26% at 5 years which is nearly as high as recurrence risk in patients with N2/N3 disease. In contrast, patients with N1 EBC without high-risk features had a recurrence risk of 11% at 5 years which is similar to N0 disease. Patients that met monarchE criteria (N1-HRG, N2, N3 EBC) had a 5-year risk of recurrence of 29%, supporting the use of adjuvant abemaciclib plus ET in these patients with high-risk EBC. Citation Format: Sara M. Tolaney, Sarah Sammons, Javier Cortes, Astra M Liepa, Tomoko Sugihara, Zhanglin Lin Cui, Wambui Gathirua-Mwangi, Brenda Grimes, Ashwin Shahir, Mauricio Monaco, Patrick Neven, Stephen Johnston. Risk of Recurrence by Nodal Status and High-Risk Features in Patients with HR+, HER2-, Early Breast Cancer: An Analysis of Real-world Data [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-11-02.