Abstract PS01-04: To dissect or not to dissect? The surgeon’s perspective on the prediction of ≥ 4 axillary lymph node metastasis in cN0 T1-2 breast cancer: A comparative analysis of the per-protocol population of the SINODAR-ONE clinical trial

Abstract Objectives The role of axillary surgery in the management of breast cancer (BC) has evolved considerably over the past decades, with only a few routine indications for axillary lymph node dissection (ALND) remaining in clinical practice. However, de-escalation of axillary surgery, especially in BC patients with 1-3 positive sentinel lymph nodes (SLNs) challenges the recently established criteria for adjuvant treatment (i.e., combination therapy with abemaciclib, endocrine therapy, and chemotherapy in patients with ≥ 4 positive nodes). The question remains as to whether these patients should undergo further ALND to determine whether ≥ 4 nodes are positive. To further investigate the latest controversies in axillary management of BC patients and predict the presence of ≥ 4 axillary lymph node metastasis, we evaluated and compared patients ≥ 4 positive nodes in the per-protocol population of the SINODAR-ONE clinical trial. Patients in the standard arm (ALND) of the per-protocol population were evaluated, and a comparison of characteristics between patients with ≥ 4 metastatic lymph nodes versus patients with 1-3 metastatic lymph nodes was performed. Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. Multivariable analysis was performed using a logistic regression model to identify independent predictors of ≥4 axillary lymph node metastasis. Results: Overall, 403 cN0 T1-2 BC patients in the per-protocol population were randomized to receive ALND. Of these, 65 and 338 patients presented with ≥ 4 or 1-3 axillary lymph node metastasis, respectively. Invasive lobular BC (26.2% versus 14.5% if other histology, odds ratio (OR)=4.185, 95% confidence interval (95%CI)= 1.284-1.443, p= 0.041), G3 (38.5% versus 21.3% if G1-2, OR=5.930, 95%CI= 2.134-2.289, p= 0.015), pT2 (46.2% versus 30.5% if pT1, OR=5.260, 95%CI= 15.330-16.346, p= 0.022), and 2 positive SLNs (32.3% versus 13.6% if 1 positive SLN, OR=13.188, 95%CI= 1.179-1.280, p 0.0001) were found to significantly increase the probability to present ≥4 axillary lymph node metastasis at definitive histopathological evaluation. Conclusions: The introduction of abemaciclib and other combination therapies has the potential to impact the surgical management of the axilla. Our results suggest that a minority of cN0 T1-2 BC patients may be understaged if ALND is not performed. However, the improvements and increasing effectiveness of combination therapies may sufficiently control and treat the axillary tumor-burden left behind, potentially reducing the need for extensive axillary surgery, as demonstrated by the promising 3-year oncological outcomes of the SINODAR-ONE trial. Although ALND may still be considered, after multidisciplinary team discussion, in individual patients presenting with specific risk factors for additional axillary disease (lobular, G3, pT2 BC with 2 positive SLNs), our suggestion is that routine ALND is not indicated for systemic therapy decision-making in the upfront surgical setting. Citation Format: Damiano Gentile, Wolfgang Gatzemeier, Andrea Sagona, Erika Barbieri, Alberto Bottini, Alberto Testori, Valentina Errico, Simone Di Maria Grimaldi, Giulia Caraceni, Shadya Darwish, Giuseppe Canavese, Corrado Tinterri. To dissect or not to dissect? The surgeon’s perspective on the prediction of ≥ 4 axillary lymph node metastasis in cN0 T1-2 breast cancer: A comparative analysis of the per-protocol population of the SINODAR-ONE clinical trial abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-04.