Galimberti V, et al. - Researchers present here the follow-up (median 9.7 years [IQR 7.8–12.7]) findings of the phase 3 IBCSG 23-01 trial, which previously showed no difference in disease-free survival at 5-years between patients with breast cancer with one or more micrometastatic (≤ 2 mm) sentinel nodes randomly assigned to either axillary dissection or no axillary dissection and showed non-inferiority of no axillary dissection relative to axillary dissection. The results of this study confirmed those obtained at 5 years and were consistent with those of the 10-year follow-up analysis of the Z0011 trial. The current practice of not doing an axillary dissection when the tumor burden in the sentinel nodes is minimal or moderate in patients with early breast cancer was supported by these findings collectively.

Methods

• This was a multicenter, randomized, controlled, open-label, non-inferiority, phase 3 trial.
• Among participants recruited from 27 hospitals and cancer centers in nine countries for this trial, the 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.
• Researchers used permuted blocks generated by a web-based congruence algorithm to randomly assign (1:1) patients before surgery (mastectomy or breast-conserving surgery) to no axillary dissection or axillary dissection, with stratification by center and menopausal status.
• Disease-free survival was analyzed in the intention-to-treat population (as randomly assigned) and represented the protocol-specified primary endpoint.
• All randomly assigned patients who received their allocated treatment (as treated) were included in the safety analysis.
• They compared the observed hazard ratios (HRs) for disease-free survival with a margin of 1.25 in order to perform a one-sided test for non-inferiority of no axillary dissection.
• This 10-year follow-up analysis was not adjusted for multiple, sequential testing as it was not prespecified in the trial's protocol.

Results

• Screening was performed in 6,681 patients between April 1, 2001, and Feb 8, 2010; randomization of 934 to no axillary dissection (n=469) or axillary dissection (n=465) was done.
• After randomization, three patients who were ineligible were excluded from the trial.
• In the no axillary dissection group vs in the axillary dissection group, the disease-free survival at 10 years was 76.8% (95% CI 72.5–81.0) vs 74.9% (70.5–79.3), respectively (HR 0.85, 95% CI 0.65–1.11; log-rank p=0.24; p=0.0024 for non-inferiority).
• The observed long-term surgical complications in no axillary dissection group vs axillary dissection group were lymphoedema of any grade [16 (4%) of 453 patients vs 60 (13%) of 447], sensory neuropathy of any grade [57 (13%) vs 85 (19%)], and motor neuropathy of any grade (14 [3%] vs 40 [9%]).
• Axillary dissection was held responsible for one serious adverse event (postoperative infection and inflamed axilla requiring hospital admission); the event resolved without sequelae.