Abstract Introduction: The SOUND and INSEMA trials included patients who underwent breast-conserving surgery (BCS). Mastectomy offers equivalent local control; however, tumor stage is often more advanced, potentially impacting adjuvant treatment decisions. Adjuvant cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) provide oncological benefits to patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC). Their indication is based on clinical parameters yet irrespective of the type of breast surgery performed. Consequently, it remains unclear whether in SOUND/INSEMA eligible patients with HR-positive/HER2-negative BC undergoing mastectomy versus BCS proportions of node-positivity differ, and whether omission of sentinel lymph node biopsy (SLNB) would impact treatment candidacy for CDK4/6i differently. Methods: This single-center, retrospective cohort study included patients with clinically T1 and T2, cN0/iN0, HR-positive/HER2-negative BC who underwent SLNB between 01/2014 and 12/2024. Clinicopathological features, nodal involvement, and CDK4/6i eligibility were compared between patients who underwent mastectomy and BCS. CDK4/6i eligibility was evaluated using the monarchE (≥4 positive lymph nodes, or 1-3 positive lymph nodes and either grade 3 disease, tumor size ≥5cm, or Ki67 ≥20%) and NATALEE inclusion criteria. 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 treatment. Multivariable logistic regression analysis was used to identify independent predictors of node-positivity and CDK4/6i eligibility. Results: A total of 454 patients were included, of whom 31.9% (145/454) underwent a mastectomy. Patients who underwent a mastectomy had clinically larger tumors (cT2 37.2% vs. 27.8%, p=0.05) without differences in pathological tumor stage (p=0.185). Tumors of patients who underwent a mastectomy were more frequently multifocal (23.5% vs. 9.7%, p0.001), of lobular histotype (21.4% vs. 11.3%, p=0.008), and exhibited a higher tumor grade (grade II and III 73.8% vs. 63.8%, p=0.019). The median number of positive lymph nodes was comparable between groups (0, IQR 0-0 vs. 0, IQR 0-0, p=0.283) without differences in pathological nodal stage (pN1 16.6% vs. 14.6%, p=0.168). Predictors of node-positivity were found to be lymphovascular invasion (odds ratio OR 6.8, 95%CI 3.7-12.9, p0.001) and premenopausal status (OR 2.0, 95%CI 1.0-3.8, p=0.034). Mastectomy was not found to be a predictor of node-positivity (OR 1.1, 95%CI 0.6-1.9, p=0.719). Eligibility for any CDK4/6i was numerically higher in patients who underwent a mastectomy (29.7% vs. 21.4%, p=0.06). However, eligibility based on nodal criteria did not show any differences between the groups (abemaciclib 7.6% vs. 6.2%, p=0.550; ribociclib 9.7% vs. 7.8%, p=0.586). Predictors for CDK4/6i eligibility were found to be ≥pT2 (OR 12.9, 95%CI 6.5-26.5, p0.001), Ki67 ≥20% (OR 5.3, 95%CI 2.9-10.0, p0.001), and lymphovascular invasion (OR 5.1, 95%CI 2.6-10.1, p0.001). Mastectomy was not found to be a predictor of CDK4/6i eligibility (OR 1.3, 95%CI 0.7-2.3, p=0.481). Conclusion: In patients with cT1-T2, cN0/iN0, HR-positive/HER2-negative BC, type of surgery did neither impact node positivity nor CDK4/6i eligibility. These findings support the consideration of SLNB omission in appropriately selected patients undergoing mastectomy, particularly postmenopausal women with low-risk tumors. Further investigation of the extension of SLNB omission eligibility to patients undergoing mastectomy is warranted. Citation Format: M. Heidinger, G. Montagna, F. Halbeisen, N. Maggi, M. Frevert, R. Kiblawi, J. Loesch, F. D. Schwab, C. Kurzeder, T. A. Zwimpfer, W. P. Weber. Patients with small, clinically and imaging node-negative, HR-positive/HER2-negative early breast cancer undergoing mastectomy do not show increased node-positivity and missed adjuvant systemic treatment options 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 PS2-01-30.
Heidinger et al. (Tue,) studied this question.