Abstract GS02-05: Overview of Axillary Treatment in Early Breast Cancer: patient-level meta-analysis of long-term outcomes among 20,273 women in 29 randomised trials

Abstract Background: In early breast cancer, the optimal management of the axilla is uncertain. To better understand the long-term benefits and risks of different approaches, we undertook an individual patient data meta-analysis of randomised trials comparing varying types of axillary treatment. Methods: Information was available on 20,273 women in 29 trials of axillary surgery or axillary radiotherapy. The trial comparisons included in this overview are summarised in Table 1. Randomisation took place during 1958–2009. Median follow-up was 10.0 years (IQR 7.4–11.5). Findings: In the trials of more extensive versus less extensive axillary treatment, the rate ratios (RR) for locoregional recurrence varied by site (p=0.003), however, 82% of these locoregional recurrences (552/670) occurred either in the breast or were of unspecified location (Table 2). Considering locoregional recurrence at any site, there was little difference in the risk from more versus less axillary treatment (10-year risk 4.3% vs 4.7%; RR 0.90 95% CI 0.77–1.05; p = 0.20), even in women treated for node-positive disease (3.7% vs 3.6%; RR 1.01, 95% CI 0.74–1.36, p=0.97). There was, however, a substantial difference in lymphoedema for trials of more versus less axillary surgery (odds ratio (OR) 2.35, 95% CI 2.05–2.70; p< 0.00001) and for trials of axillary treatment (surgery or radiotherapy) compared with no further axillary treatment (OR 3.08, 95% CI 2.01–4.71; p< 0.00001). In the four trials comparing axillary node clearance to axillary radiotherapy, the risk of locoregional recurrence appeared to be somewhat reduced in women allocated to clearance (43 vs. 56 events, 10-year risk 4.4% vs. 6.9%; RR 0.64, 95% CI 0.43-0.96, p=0.03) whilst their risk of lymphoedema was increased (OR 1.79, 95% CI 1.42–2.27; p< 0.00001). The risks of distant recurrence, breast cancer, non-breast-cancer, or all-cause mortality did not differ significantly by extent of axillary treatment or when comparing axillary clearance to radiotherapy. Interpretation: This is the most comprehensive overview of axillary treatment to date. Less extensive surgery, such as sentinel lymph node biopsy, or using axillary radiotherapy, resulted in a substantial reduction in lymphoedema compared to axillary node clearance. While there was no evidence of a difference in locoregional recurrence, a moderate effect cannot be excluded. Funding: Cancer Research UK, British Heart Foundation, Medical Research Council Table 1: Summary of the trials of treatment of the axilla in early breast cancer that began prior to 2012. Table 2: Numbers of locoregional recurrences as first event and rate ratios in the trials of more versus less axillary treatment. Citation Format: Gurdeep Mannu, Graham Beake, Richard Berry, David Dodwell, Robert Hills, Paul McGale, Stewart Anderson, Ian Campbell, Armando E. Giuliano, Reshma Jagsi, Thorsten Kuehn, Rebecca Llewellyn-Bennett, Eleftherios Mamounas, Robert Mansel, Pascal Roy, Emiel Rutgers, Nisha Sharma, Sandra Swain, Jonas Bergh, On behalf of the EBCTCG. Overview of Axillary Treatment in Early Breast Cancer: patient-level meta-analysis of long-term outcomes among 20,273 women in 29 randomised trials [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-05.