Abstract PD15-11: PD15-11 Axillary dissection to determine nodal burden to inform systemic therapy recommendations in patients with clinically node-positive breast cancer: Pre-planned substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101)

Abstract Introduction: Chemotherapy is recommended for patients with luminal breast cancer and more than three positive nodes. In addition, recent landmark trials raised the question if the exact number of positive nodes is required to indicate genomic testing. In the neoadjuvant setting, response-driven therapy is increasingly used and may be influenced by surgical staging of the axilla. The present study addressed the role of axillary lymph node dissection (ALND) as decision aid for systemic therapy in a contemporary cohort of patients with clinically node-positive breast cancer in the adjuvant and neoadjuvant setting. Methods: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614). The first 500 patients with clinically node-positive breast cancer who were randomized after tailored axillary surgery (TAS) to undergo ALND or axillary radiotherapy (ART) without ALND in the context of extended regional irradiation were included from August 2018 to June 2022. Clinically node-positive breast cancer was defined by confirmed nodal disease at the time of initial diagnosis; in case of neoadjuvant therapy, the finding of residual nodal disease was mandatory for randomization. TAS consisted of removal of palpably suspicious findings and the sentinel nodes with the option of image guidance. In the ART arm, the total number of positive nodes was not known. We analyzed the impact of ALND on rate and type of systemic therapy. Results: A total of 500 patients with a median age of 57 years (IQR: 48-69 years) were included at 44 breast centers from six European countries. Subtype was hormone receptor (HR) positive (+) and human epidermal growth factor receptor 2 (HER2) negative (-) in 393 (80.0%), HR+/HER2+ in 52 (10.6%), HR-/HER2+ in 5 (1.0%) and HR-/HER2- in 34 (6.9%) patients. Of 343 patients (68.6%) who were treated in the adjuvant setting, 297 had HR+/HER2- disease. Of these 297 patients, 145 (48.8%) underwent ART without ALND and 152 (51.2%) underwent ALND after TAS. In the ART arm, the median number of lymph nodes removed was five (IQR 4-8), three (IQR 1-4) of which were positive and in the ALND arm, the number was 19 (IQR 14-26), four (IQR 2-9) of which were positive (p < 0.001). The use of ALND had no significant impact on the rate of patients with HR+/HER2- disease undergoing adjuvant chemotherapy (51.0% in the ART and 57.9% in the ALND arm, p=0.2), and there were no significant differences in type of systemic therapy with the exception of tamoxifen, which was 18.4% with ALND versus 9.0% without (p=0.018). A total of 143 patients (28.6%) underwent neoadjuvant chemotherapy, 13 had neoadjuvant antihormonal treatment and one had neoadjuvant double HER2-blockade without chemotherapy. Of the 143 patients who received neoadjuvant chemotherapy, 71 (49.7%) underwent ART without ALND and 72 (50.3%) underwent ALND. In the ART arm, the median number of lymph nodes removed was four (IQR 3-6), one (IQR 1-3) of which was positive and in the ALND arm, the number was 16 (IQR 12-19), two (IQR 1-5) of which were positive (p < 0.001). The use of ALND in patients after neoadjuvant treatment had no significant impact on the rate of adjuvant systemic therapy (71.8% in the ART and 65.3% in the ALND arm, p=0.4), with no significant differences in type of chemotherapy (e.g., capecitabine: 11.3% vs 12.5%, p=0.8; T-DM1: 11.3% vs. 11.1%, p>0.9) or antihormonal therapy (e.g., aromatase inhibitors: 49.3% vs. 41.7%, p=0.4; tamoxifen: 11.3% vs. 5.6%, p=0.2). Discussion: This study showed that although ALND significantly increased the number of positive nodes removed in the adjuvant and neoadjuvant setting, it had no relevant impact on rate and type of adjuvant systemic therapy. Citation Format: Walter P. Weber, Zoltan Matrai, Stefanie Hayoz, Christoph Tausch, Guido Henke, Daniel R. Zwahlen, Günther Gruber, Frank Zimmermann, Thomas Ruhstaller, Simone Muenst, Markus Ackerknecht, Sherko Küemmel, Vesna Bjelic-Radisic, Viktor Smanykó, Conny Vrieling, Rok Satler, Inna Meyer, Charles Becciolini, Susanne Bucher, Colin Simonson, Peter M. Fehr, Natalie Gabriel, Robert Maráz, Dimitri Sarlos, Konstantin J. Dedes, Cornelia Leo, Gilles Berclaz, Hisham Fansa, Christopher Hager, Klaus Reisenberger, Ákos Sávolt, Christian F. Singer, Roland Reitsamer, Jelena Winkler, Giang Thanh Lam Lam, Mathias K. Fehr, Tatiana Naydina, Magdalena Kohlik, Karine Clerc, Valerijus Ostapenko, Florian Fitzal, Martin Heidinger, Nadia Maggi, Alexandra Schulz, Pagona Markellou, Loïc Lelièvre, Daniel Egle, Jörg Heil, Michael Knauer, Christian Kurzeder. PD15-11 Axillary dissection to determine nodal burden to inform systemic therapy recommendations in patients with clinically node-positive breast cancer: Pre-planned substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-11.