Article,
Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases
Contributors
De Boniface, Jana Marit
0000-0001-9518-0902
[1]
[2]
[3]
Rydén, Lisa
0000-0001-7515-3130
[1]
[2]
[3]
Kontos, Michalis I
0000-0003-1686-7875
[1]
[2]
[3]
Gentilini, Oreste Davide
0000-0002-4489-1867
[1]
[2]
[3]
Olofsson Bagge, Roger
0000-0001-5795-0355
[1]
[2]
[3]
Sund, Malin Åsa Margareta
0000-0002-7516-9543
[1]
[2]
[3]
Appelgren, Matilda
0000-0003-3965-5568
[1]
[2]
[3]
Ahlgren, Johan
0000-0001-6392-273X
[1]
[2]
[3]
Sackey, Helena Ikonomidis
0009-0005-5320-0246
[1]
[2]
[3]
Vikhe Patil, Eva
0000-0001-9441-4420
[1]
[2]
[3]
Andersson, Yvette
0000-0003-0347-2196
[1]
[2]
[3]
Bergkvist, Leif Å
0000-0002-8054-8847
[1]
[2]
[3]
Affiliations
- [1] From the Departments of Molecular Medicine and Surgery (J.B., M.A., H.S., J.F.) and Medical Epidemiology and Biostatistics (R.S.), Karolinska Institutet, the Department of Surgery, Capio St. Göran's Hospital (J.B., M.A., S.N.), Cytel (R.S.), the Department of Surgery, Södersjukhuset (F.C.), and Breast Center Karolinska, Karolinska Comprehensive Cancer Center, Karolinska University Hospital (H.S., J.F.), Stockholm, the Faculty of Medicine, Institute of Clinical Sciences, Lund University (L.R., S.A.), and the Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital Lund (S.A.), Lund, the Department of Gastroenterology and Surgery (L.R.), and Radiation Physics, Department of Hematology, Oncology, and Radiation Physics (E.W.), Skåne University Hospital Lund, Malmö, the Departments of Surgery (R.O.B.) and Oncology (D.L.), Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, and the Departments of Surgery (R.O.B.) and Oncology (D.L.), Sahlgrenska University Hospital, Gothenburg, the Department of Diagnostics and Intervention-Surgery, Umeå University, Umeå (M.S.), the Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro (J.A.), Regional Cancer Center of Mid-Sweden, Uppsala (J.A.), the Department of Surgery, Skaraborg Hospital, Lidköping (P.F.N.), the Department of Biomedical and Clinical Sciences (E.V.P.), Linköping University, and the Department of Surgery, Linköping University Hospital (E.V.P.), Linköping, and the Department of Surgery (Y.A.) and the Center for Clinical Research, Uppsala University and Region Vastmanland, Vastmanland Hospital (Y.A., L.B.), Vasteras - all in Sweden; the Faculty of Health and Medical Sciences, University of Copenhagen (T.F.T.), the Department of Breast Surgery, Gentofte Hospital, Gentofte (T.F.T.), the Department of Surgery, Breast Clinic, Viborg Hospital, Viborg (I.S.A.), the Department of Plastic and Breast Surgery, Aalborg University Hospital, Aalborg (U.H.), the Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle (H.D.N.), and the Departments of Oncology (B.V.O.) and Plastic and Breast Surgery (P.C.), Aarhus University Hospital, the Departments of Oncology (B.V.O.) and Clinical Medicine (P.C.), Aarhus University, and the Department of Experimental Clinical Oncology, Danish Center for Particle Therapy (B.V.O.), Aarhus - all in Denmark; the Department of Obstetrics and Gynecology, University of Rostock, Rostock (T.R.), the Breast Center, Die Filderklinik, Filderstadt (T.K.), and the Department of Gynecology and Obstetrics, University of Ulm, Ulm (T.K.) - all in Germany; the First Department of Surgery, National and Kapodistrian University of Athens, Athens (M.K.); the Department of Breast Surgery, IRCCS Ospedale San Raffaele (O.D.G.), and Vita-Salute San Raffaele University (O.D.G.) - both in Milan; and the Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki (M.S.). [NORA names: Denmark; Europe, EU; Nordic; OECD];
- [2] Karolinska Institutet [NORA names: Sweden; Europe, EU; Nordic; OECD];
- [3] National and Kapodistrian University of Athens [NORA names: Greece; Europe, EU; OECD]
Abstract
BACKGROUND: Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups. METHODS: We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44. RESULTS: Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy-only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy-only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin. CONCLUSIONS: The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).
