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Clinical Trial
. 2023 Oct 1;158(10):1013-1021.
doi: 10.1001/jamasurg.2023.2840.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer

Walter P Weber  1   2 , Zoltan Matrai  3 , Stefanie Hayoz  4 , Christoph Tausch  5 , Guido Henke  6   7 , Frank Zimmermann  2   8 , Giacomo Montagna  9 , Florian Fitzal  10   11 , Michael Gnant  11   12 , Thomas Ruhstaller  2   13 , Simone Muenst  2   14 , Andreas Mueller  4   15 , Loïc Lelièvre  16 , Jörg Heil  17 , Michael Knauer  13 , Daniel Egle  12   18 , Ákos Sávolt  19 , Martin Heidinger  1   2 , Christian Kurzeder  1   2 ; TAXIS Study Writing Group; Daniel R Zwahlen  20 , Günther Gruber  21 , Markus Ackerknecht  2   22 , Sherko Kuemmel  23   24 , Vesna Bjelic-Radisic  25 , Viktor Smanykó  26 , Conny Vrieling  27 , Rok Satler  15 , Daniela Hagen  15 , Charles Becciolini  28 , Susanne Bucher  29 , Colin Simonson  30 , Peter M Fehr  31 , Natalie Gabriel  32 , Robert Maráz  33 , Dimitri Sarlos  34 , Konstantin J Dedes  35 , Cornelia Leo  36 , Gilles Berclaz  37 , Hisham Fansa  38 , Christopher Hager  12   39 , Klaus Reisenberger  12   40 , Christian F Singer  12   41 , Sibylle Loibl  42 , Jelena Winkler  43 , Giang Thanh Lam  44 , Mathias K Fehr  45 , Magdalena Kohlik  46 , Karine Clerc  47 , Valerijus Ostapenko  48 , Nadia Maggi  1   2 , Alexandra Schulz  2   49 , Mariacarla Andreozzi  1   2 , Maite Goldschmidt  1   2 , Ramon Saccilotto  2   49 , Pagona Markellou  7
Affiliations
Clinical Trial

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer

Walter P Weber et al. JAMA Surg. .

Abstract

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown.

Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT).

Design, setting, and participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required.

Exposures: All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators.

Results: A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]).

Conclusion: Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Weber reported receiving grants from the Swiss State Secretary for Education, Research and Innovation, the Swiss Cancer Research Foundation, the Swiss Cancer League, Fond’Action Contre le Cancer, Rising Tide Foundation for Clinical Cancer Research, Cancer League Basel, the Claudia von Schilling Foundation for Breast Cancer Research, Kaempf-Bötschi Foundation, Cancer League Zentralschweiz, Cancer League Thurgau, Cancer League Wallis, Cancer League Aargau, Giuliana and Giorgio Stefanini Foundation, Miaso foundation, Krebsbekämpfung Foundation, Moritz Straus-Foundation, Freiwillige Akademische Gesellschaft, Association Marianne Payot, J&K Wonderland Foundation, SANA Foundation, Fondation pour la Recherche et le Traitement Médical, SPS Foundation, Domarena Foundation, and Agendia during the conduct of the study. Dr Fitzal reported receiving personal fees from Novartis, AstraZeneca, Roche, and MSD outside the submitted work. Dr Gnant reported receiving personal fees from AstraZeneca, from Daiichi Sankyo, Eli Lilly and Company, Menarini-Stemline, MSD, Novartis, Pierre Fabre, and Verachte outside the submitted work and having an immediate family member employed by Sandoz during the conduct of the study. Dr Muenst reported receiving speaker fees from GSK Consumer Healthcare and advisory board fees from Novartis and Diaceutics outside the submitted work. Dr Mueller reported receiving stock options from Vifor; personal fees from Lilly, Novartis, Pfizer, Genomic Health, AstraZeneca, Daiichi Sankyo, Roche, Pierre Fabre, Exact Sciences, Myriad Genetics, Gilead Sciences, GSK Consumer Healthcare, MSD; and grants from Roche outside the submitted work. Dr Knauer reported receiving grants from Agendia and Swiss Cancer Research and advisory board fees from Myriad outside the submitted work. Dr Egle reported receiving personal fees from AstraZeneca, Daiichi Sankyo, Gilead, MSD, Novartis Pfizer, and Sirius and nonfinancial support from Roche outside the submitted work. Dr Kurzeder reported receiving grants from Swiss Cancer Research; personal fees and nonfinancial support from GSK Consumer Healthcare, AstraZeneca, Novartis, Pharmamar, Roche; and personal fees from Genomic Health, Eli Lilly and Company, Merck, MSD, Pfizer, and Daichii Sankyo outside the submitted work. Dr Zwahlen reported receiving patient fees from Swiss Group for Clinical Cancer Research during the conduct of the study. Dr Kuemmel reported receiving personal fees from Roche/Genentech, Genomic Health, Novartis, AstraZeneca, Amgen, Celgene, Somatex, Daiichi Sankyo, PFM Medical, Pfizer, MSD Oncology, Eli Lilly and Company, Sonoscape, Gilead Sciences, Seagen, Agendia; and travel/accommodation expenses from Roche, Daiichi Sankyo, and Sonoscape outside the submitted work. Dr Smanykó reported receiving personal fees from Swiss Group for Clinical Cancer Research during the conduct of the study. Dr Gabriel reported receiving grants from University Basel and Swiss Group for Clinical Cancer Research Study and patient fees for the TAXIS study during the conduct of the study. Dr Berclaz reported receiving patient fees from the University of Basel during the conduct of the study. Dr Singer reported receiving personal fees from Novartis; nonfinancial support from AstraZeneca, Daiichi Sankyo, Roche, and Sagen and grants from Amgen during the conduct of the study. Dr Loibl reported receiving grants, advisory board fees, and speaker fees from AstraZeneca, Gilead, BMS/Celgene, Novartis, Pfizer, and Seagen; grants from AbbVie, DSI, Molecular Health and Roche; speaker fees from Amgen, Sanofi, Relay, Olema, Incyte, Roche, Merck KG, Eli Lilly and Company, and GSK Consumer Healthcare; medical writing support from AstraZeneca, Pfizer, Roche, Novartis, DSI, and Cellcuity; and having a patent for VM Scope with royalties paid to institute, a patent for EP14153692.0 pending, a patent for EP21152186.9 pending, and a patent for EP15702464.7 pending. Drs Schulz, Andreozzi, and Goldschmidt reported receiving payment for clinical project management work within the TAXIS study. Dr Saccilotto reported receiving funds to support research groups from University of Basel Special Funds during the conduct of the study. No other disclosures were reported.

Comment in

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