Abstract Introduction The SOUND and INSEMA trials demonstrated that sentinel lymph node biopsy (SLNB) can be safely omitted in patients with small, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) who are clinically and imaging node-negative (cN0/iN0). However, recruitment for these trials ended prior to the approval of adjuvant cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, which rely in part on nodal status for eligibility. Therefore, the extent to which SLNB omission impacts eligibility for CDK4/6 inhibitors and consequently oncological outcomes is unknown. Methods This was a single-center, retrospective cohort study of patients with clinically T1 and T2, cN0/iN0, HR-positive/HER2-negative BC who underwent breast-conserving surgery with a SLNB between 01/2014-12/2024. Preoperative axillary ultrasound was used throughout the study period. CDK4/6 inhibitor eligibility was estimated based on the monarchE and NATALEE inclusion criteria. Abemaciclib eligibility included patients with ≥4 positive lymph nodes, or 1-3 positive lymph nodes and either grade 3 disease, tumor size ≥5cm, or Ki67 ≥20%. Ribociclib eligibility based on node-criteria was defined as either pT1pN1 (excluding pN1mi) or pT2pN1, provided that no additional criteria would render the pT2 status per se eligible for ribociclib treatment. Predictors of CDK4/6 inhibitor eligibility and node-positivity were identified utilizing multivariable logistic regression models. Estimates of the impact on invasive disease-free survival are based on the five- and three-year results of the monarchE and NATALEE trials, respectively. Results Of 309 patients, 78.3% (242/309) were postmenopausal, 28.8% (89/309) had a ≥pT2 tumor, and 14.6% (45/309) had pN1 disease. 21.4% (66/309) qualified for adjuvant CDK4/6 inhibitor treatment. 6.1% (19/309) were eligible for abemaciclib and 7.8% (24/309) were eligible for ribociclib based on node criteria. Consequently, 17 (95%CI 11-27) and 13 (95%CI 9-20) patients would be required to undergo SLNB in order to identify one patient qualifying for abemaciclib and ribociclib (based on node-criteria), respectively. Predictors of CDK4/6 inhibitor eligibility were found to be pathological tumor stage ≥pT2 (odds ratio OR 10.3, 95%CI 4.5-25.1, p0.001), Ki67 ≥20% (OR 4.9, 95%CI 2.3-10.5, p0.001), and lymphovascular invasion (OR 4.6, 95%CI 2.0-10.7, p0.001). Lymphovascular invasion (OR 5.3, 95%CI 2.4-11.5, p0.001) was found as the sole predictor for node-positivity. Based on the 5-year monarchE (NNT=28) and 3-year NATALEE (NNT=63) data, it was estimated that 3 (95%CI 2-4) and 2 (95%CI 1-2) patients, out of 1000, would experience a recurrence upon omission of the SLNB due to lack of candidacy for abemaciclib and ribociclib, respectively.A subgroup analysis of patients with cT1 tumors (n=223) demonstrated that 4.5% (10/223) of patients were eligible for abemaciclib and 8.1% (18/223) for ribociclib based on node-criteria. The number of patients required to undergo a SLNB was 23 (95%CI 13-47) and 13 (95%CI 9-21) for eligibility for abemaciclib and ribociclib (based on node criteria), respectively. Omission of SLNB in a collective of 1000 patients would result in 3 (95%CI 1-3) and 2 (95%CI 1-2) patients experiencing recurrences due to missed treatment with abemaciclib and ribociclib, respectively. Conclusion Omission of SLNB in patients with small HR+/HER2- tumors results in a missed indication for CDK4/6 inhibitors in 10% of patients with minimal impact on recurrence. SLNB should not routinely be performed in patients who meet SOUND/INSEMA criteria. Citation Format: M. Heidinger, T. A. Zwimpfer, F. Halbeisen, N. Maggi, M. Frevert, R. Kiblawi, J. M. Loesch, F. D. Schwab, C. Kurzeder, G. Montagna, W. P. Weber. Omission of sentinel lymph node biopsy in early stage HR-positive HER2-negative breast cancer: impact on adjuvant CDK4/6 inhibitor candidacy and oncological outcomes abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD12-03.
Heidinger et al. (Tue,) studied this question.