1. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled, phase 3 trial
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Achim Fleischmann, Cindy Mak, Jane Hill, David Littlejohn, Andreas Veronesi, Holger Moch, Stefano Zurrida, L Perey, Nirmala Pathmanathan, Carlo Tondini, Giancarlo Pruneri, Viviana Galimberti, Christian Oehlschlegel, Christoph Rageth, Jack Hoffmann, Richard D. Gelber, John J. Collins, Angelo Recalcati, Marisa Donatella Magri, Andrée Rorive, Bruno Späti, Dimitri Sarlos, Zsuzsanna Varga, Rolf A. Stahel, Mattia Intra, Charlotte Lanng, P. Smart, L. Tan, Anna Cardillo, Francesco Coran, James French, Rudolf Maibach, Manuela Rabaglio, Marco Colleoni, Emilia Montagna, Elisabeth Saurenmann, Elisabeth Elder, Michael Knauer, Samuele Massarut, Mauro Arcicasa, Karin Ribi, Julie Craik, Theresa Zielinski, Wendy Jeanneret Sozzi, Sandro Morassut, Tiziana Rusca, Paul Chin, Elgene Lim, Frances M. Boyle, Richard West, Patrizia Dell'Orto, Umberto Veronesi, Marie-Christine Mathieu, Jean-Remi Garbay, Katrina Moore, Marisa Cristina Leonardi, Gregory Bruce Mann, Donatella Santini, Mario Roncadin, Joëlle Collignon, Michael D. Green, David Moon, Oreste Gentilini, Petere G. Gill, Stephen Allpress, Giulia Peruzzotti, Elga Majdic, Caitlin Mahoney, Karen N. Price, Craig Murphy, Lori Hayes, Melissa Bochner, Lynette Mann, Christoph Tausch, Otto Schiltknecht, Antonino Carbone, Aron Goldhirsch, Giuseppe Cancello, Anand Murugasu, John F. Forbes, Erica Piccoli, Luca Mazzucchelli, Alberto Gianatti, Lucien Zaman, Jose Manuel Cotrina, Per Karlsson, Janez Zgajnar, Diana Crivellari, Birgitte Bruun Rasmussen, Elisabetta Candiago, Manuela Sargenti, Robert Whitfield, Silvia Dellapasqua, R. Ghisini, Meredith M. Regan, Michael Müller, Tiziana Perin, M. Thorburn, Stamatina Fournarakou, Monika Bamert, Malcolm Buchanan, Allison Jones, Gerhard Ries, Andreas Ehrsam, Hugh Carmalt, István Láng, Jürg Bernhard, Guy Jerusalem, Manuela Lagrassa, S. Fiona Bonar, Mario Mileto, Jurij Lindtner, P. Jeal, Fereshte Farshidi, Bernard F. Cole, John Hoerby, James Kollias, Privato Fenaroli, Giovanni Mazzarol, Richard Dyer, Angelo Buonadonna, Heidi Roschitzki, Stefania Andrighetto, Robert Macindoe, Martin F. Fey, Ingrid Kössler, Olivia Pagani, Anita Hiltbrunner, Camelia Chifu, William Ross, Rachele Volpe, Linda Leidi, Barbara Ruepp, Giorgio Caccia, Philippe Delvenne, Susanne Gerred, Tara Scolese, Mario Taffurelli, Paola Baratella, Jean Francois Delaloye, Richard Harman, A. Michael Bilous, Ian G. Campbell, Franco Nolè, Maryse Fiche, Ute Lorenz, Susanne Roux, Roberto Orecchia, Mark Sywak, Aashit Shah, Assia Treboux, Laura Cattaneo, Martina Egli-Tupaj, Rosmarie Caduff, Paolo Veronesi, Linda Madigan, Elena Kralidis, Maj-Lis Moeller Talman, Roswitha Kammler, Michael Töpfer, Eva Juhasz, Peer Schousen, Michele Ghielmini, Snjezana Frkovic-Grazio, Hanne Galatius, Elisabeth Rippy, Sylvie Maweja, Lynette Blacher, Stefan Aebi, D.F. Preece, Gilles Berclaz, Daniel Wyss, D. F. Lindsay, Andreas Günthert, Frederick Mayall, Lucia Bronz, Paul McKenzie, Andrew J. Spillane, Giuseppe Viale, Sandra Lippert, Alberto Luini, Virginia Howard, Giuseppe Curigliano, Rainer Grobholz, Robert Millar, Julio Abugattas, Hans-Anton Lehr, Maria Emanuela Limonta, Monica Iorfida, Elisa Vicini, Helle Holtveg, Angelo Di Leo, Giuseppe Renne, Alan S. Coates, Ezio Candiani, Karolyn Scott, Mauro G. Mastropasqua, Paolo Tricomi, Thomas Gyr, Karen Briscoe, and Viviana Galimberti, Bernard F Cole, Giuseppe Viale, Paolo Veronesi, Elisa Vicini, Mattia Intra, Giovanni Mazzarol, Samuele Massarut, Janez Zgajnar, Mario Taffurelli, David Littlejohn, Michael Knauer, Carlo Tondini, Angelo Di Leo, Marco Colleoni, Meredith M Regan, Alan S Coates, Richard D Gelber, Aron Goldhirsch
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0301 basic medicine ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Population ,Breast Neoplasms ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Clinical endpoint ,Medicine ,Humans ,education ,Mastectomy ,education.field_of_study ,business.industry ,Sentinel Lymph Node Biopsy ,Hazard ratio ,Sentinel node ,medicine.disease ,Breast cancer, axillary dissection, IBCSG 23-01, follow up ,Surgery ,Clinical trial ,Axilla ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Neoplasm Micrometastasis ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Disease Progression ,Lymph Node Excision ,Female ,Sentinel Lymph Node ,business - Abstract
Summary Background We previously reported the 5-year results of the phase 3 IBCSG 23-01 trial comparing disease-free survival in patients with breast cancer with one or more micrometastatic (≤2 mm) sentinel nodes randomly assigned to either axillary dissection or no axillary dissection. The results showed no difference in disease-free survival between the groups and showed non-inferiority of no axillary dissection relative to axillary dissection. The current analysis presents the results of the study after a median follow-up of 9·7 years (IQR 7·8–12·7). Methods In this multicentre, randomised, controlled, open-label, non-inferiority, phase 3 trial, participants were recruited from 27 hospitals and cancer centres in nine countries. Eligible women could be of any age with clinical, mammographic, ultrasonographic, or pathological diagnosis of breast cancer with largest lesion diameter of 5 cm or smaller, and one or more metastatic sentinel nodes, all of which were 2 mm or smaller and with no extracapsular extension. Patients were randomly assigned (1:1) before surgery (mastectomy or breast-conserving surgery) to no axillary dissection or axillary dissection using permuted blocks generated by a web-based congruence algorithm, with stratification by centre and menopausal status. The protocol-specified primary endpoint was disease-free survival, analysed in the intention-to-treat population (as randomly assigned). Safety was assessed in all randomly assigned patients who received their allocated treatment (as treated). We did a one-sided test for non-inferiority of no axillary dissection by comparing the observed hazard ratios (HRs) for disease-free survival with a margin of 1·25. This 10-year follow-up analysis was not prespecified in the trial's protocol and thus was not adjusted for multiple, sequential testing. This trial is registered with ClinicalTrials.gov, number NCT00072293. Findings Between April 1, 2001, and Feb 8, 2010, 6681 patients were screened and 934 randomly assigned to no axillary dissection (n=469) or axillary dissection (n=465). Three patients were ineligible and were excluded from the trial after randomisation. Disease-free survival at 10 years was 76·8% (95% CI 72·5–81·0) in the no axillary dissection group, compared with 74·9% (70·5–79·3) in the axillary dissection group (HR 0·85, 95% CI 0·65–1·11; log-rank p=0·24; p=0·0024 for non-inferiority). Long-term surgical complications included lymphoedema of any grade in 16 (4%) of 453 patients in the no axillary dissection group and 60 (13%) of 447 in the axillary dissection group, sensory neuropathy of any grade in 57 (13%) in the no axillary dissection group versus 85 (19%) in the axillary dissection group, and motor neuropathy of any grade (14 [3%] in the no axillary dissection group vs 40 [9%] in the axillary dissection group). One serious adverse event (postoperative infection and inflamed axilla requiring hospital admission) was attributed to axillary dissection; the event resolved without sequelae. Interpretation The findings of the IBCSG 23-01 trial after a median follow-up of 9·7 years (IQR 7·8–12·7) corroborate those obtained at 5 years and are consistent with those of the 10-year follow-up analysis of the Z0011 trial. Together, these findings support the current practice of not doing an axillary dissection when the tumour burden in the sentinel nodes is minimal or moderate in patients with early breast cancer. Funding International Breast Cancer Study Group.
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- 2018