GPP6 - 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 multicenter randomized clinical trial
Breast Unit, IRCCS Humanitas Research Hospital European Society of Surgical Oncology (ESSO) Rozzano, Milan, Lombardia, Italy
Introduction: 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.
Methods: 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.
Conclusion: 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.
