Abstract Background: Targeted Axillary Dissection (TAD), which combines sentinel lymph node biopsy with excision of a pre-marked target lymph node, has been shown in clinical trials to improve staging accuracy and reduce false-negative rates in patients with early breast cancer (EBC) and clinically positive lymph nodes (cN+) undergoing neoadjuvant systemic therapy (NAST). By identifying NAST responders with limited residual nodal burden, TAD would enable omission of ALND in selected cases, thus reducing surgical morbidity. However, its potential applicability and impact in unselected real-world populations remain unclear. Methods: Using data from the CANTO cohort (NCT01993498), a large French prospective study including patients with stage I-III EBC, we consecutively identified patients with cT1-T4 cN+ EBC treated with NAST between May 2012 and August 2022 who underwent ALND according to national guidelines implemented during the same period. The primary outcome was the proportion of patients who would have avoided ALND if TAD had been available, defined as the percentage of patients with cN+ EBC treated with NAST who achieved axillary pCR, according to changes in surgical management of the axilla consistent with ongoing international trials (NCT05462457, NCT04373655, NCT06092892, NCT04744506) and future guideline proposals. Additional outcomes included 3-year and 5-year rate of axillary recurrence, any invasive recurrence and the impact of ALND on quality of life (QoL) using arm symptom score on QLQ BR23. Results: In total, 370 patients with cN+ EBC treated with NAST in the CANTO cohort were included, of whom 56 (15.1%) stage T1, 220 (59.5%) T2, 94 (25.4%) T3. Most of them were N1 (335 pts, 90.5%), 32 (8.7%) N2 and 3 (0.8%) N3. Pathological axillary response was available for 241 patients and 82/241 (34.0%) achieved complete pathological axillary response. Rates of complete response by BC subtype were as follows: 23/65 (35.4%) with HR-/HER2-, 37/76 (48.7%) with HER2+ and 22/100 (22.0%) with HR+/HER2- EBC. Pathological breast response was available for 255 patients and 100/255 (39.2%) had complete breast pCR. A dissociated pCR (axilla-breast) was observed in 62 patients of whom, 37 with residual cancer in axilla and 25 in the breast. Adjuvant treatments were: 356 (96.2%) locoregional radiotherapy, 27 (7.3%) chemotherapy, 224 (60.7%) hormonotherapy, 1 (0.3%) immunotherapy, 28 (7.6%) HER2-directed therapy (TDM-1, pertuzumab, trastuzumab). At a median follow-up of 93 months, 3 year-DFS was 78.3% (95%CI,73.8%;82.2%), with axillary recurrence 7.3% (n= 19/101 (18.8%) with HR-/HER2-, n= 2/122 (1.6%) with HER2+ and n=6/146 (4.1%) with HR+/HER2-; p0.001), local recurrence 2.4%, distant relapse 16.5%. 5 year-DFS was 72.2% (95%CI, 67.2%; 76.5%), with axillary recurrence 8.4% (n=19/101 (18.8%) with HR-/HER-, n=3/122 (2.5%) with HER2+ and n=9/146 (6.2%) with HR+/HER2-; p0.001), local recurrence 3.2%, distant relapse 20.8%. Overall, 108/323 (33.4%) patients experienced lymphoedema/arm pain after ALND. Conclusions: This analysis showed that TAD could have been considered instead of ALND in around one third of patients treated with NAST, particularly those with HR-/HER2- or HER2+ EBC, having a higher likelihood of complete pathological response in the axilla. These findings underline the potential of TAD to replace ALND, especially when guided by clinical response and tumor subtype. Bibliography: 1. Vaz-Luis I. ESMO Open. 2019;4(5):e000562. 2. Kuemmel S. Ann Surg. 2022 Nov 1;276(5):e553-e562. 3. Cabioglu. Ann Surg Oncol. 2025 Feb;32(2):952-966. 4. Zatecky L. World Journal of Surg Oncol, (2023) 21:252. 5. Nijveldt JJ. Ann Surg Oncol. 2024 Jul;31(7):4477-4486. 6. Kuemmel S. JAMA Surg. 2023 Aug 1;158(8):807-815 Citation Format: A. Conversano, F. Loi, J. Blanc, E. El Rassy, A. Di Meglio, J. M Ribeiro, A. Viansone, A. Puchar, J. Zeitoun, A. Turpin, A. Martin, M. Fournier, M. Gutowski, C. Cheymol, B. Sauterey, P. Cottu, A. Bertaut, B. Pistilli. Targeted Axillary Dissection after Neoadjuvant Systemic Chemotherapy in patients with Early Breast Cancer: Estimating the Real-World Impact of Omitted Axillary Lymph Node Dissection using the Canto Cohort 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 PS2-01-18.
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Angelica Conversano
Institut Gustave Roussy
Francesco Loi
J. Blanc
Clinical Cancer Research
Institut Gustave Roussy
Institut Curie
Institut Bergonié
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synapsesocial.com/papers/6996a898ecb39a600b3ef85e — DOI: https://doi.org/10.1158/1557-3265.sabcs25-ps2-01-18