Viviana Galimberti1, Bernard F Cole2, Giuseppe Viale3, Paolo Veronesi4, Elisa Vicini5, Mattia Intra5, Giovanni Mazzarol6, Samuele Massarut7, Janez Zgajnar8, Mario Taffurelli9, David Littlejohn10, Michael Knauer11, Carlo Tondini12, Angelo Di Leo13, Marco Colleoni5, Meredith M Regan14, Alan S Coates15, Richard D Gelber16, Aron Goldhirsch17. 1. Division of Senology, IEO, European Institute of Oncology IRCCS, Milan, Italy. Electronic address: viviana.galimberti@ieo.it. 2. IBCSG Statistical Center and Department of Mathematics and Statistics, University of Vermont, Burlington, VT, USA. 3. International Breast Cancer Study Group (IBCSG) Central Pathology Office, Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan, Italy; University of Milan, Milan, Italy. 4. Division of Senology, IEO, European Institute of Oncology IRCCS, Milan, Italy; University of Milan, Milan, Italy. 5. Division of Senology, IEO, European Institute of Oncology IRCCS, Milan, Italy. 6. International Breast Cancer Study Group (IBCSG) Central Pathology Office, Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan, Italy. 7. Centro di Riferimento Oncologico, Aviano, Italy. 8. Department of Surgical Oncology, Institute of Oncology, Ljubljana, Slovenia. 9. Orsola Hospital and University of Bologna, Bologna, Italy. 10. Riverina Cancer Care Centre, Wagga Wagga, NSW, Australia. 11. Breast Center St Gallen, Kantonsspital, St Gallen, Switzerland. 12. Department of Medical Oncology, Ospedale Papa Giovanni XXIII, Bergamo, Italy. 13. Hospital of Prato-AUSL Toscana Centro, Istituto Toscano Tumori, Prato, Italy. 14. IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 15. IBCSG and University of Sydney, Sydney, NSW, Australia. 16. IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Harvard T H Chan School of Public Health, Boston, MA, USA; Frontier Science and Technology Research Foundation, Boston, MA, USA. 17. IBCSG and European Institute of Oncology, Milan, Italy.
Abstract
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.
RCT Entities:
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.
Authors: Fabian Riedel; Jörg Heil; Manuel Feißt; Mahdi Rezai; Mareike Moderow; Christof Sohn; Florian Schütz; Michael Golatta; André Hennigs Journal: Breast Cancer Res Treat Date: 2019-06-24 Impact factor: 4.872