Table 1.
Landmark trials informing the de-escalation of axillary surgery in breast cancer patients.
| Trial | n patients | Recruitment Time Period | Inclusion criteria | Investigation | % of patients receiving ALND and having ≥1 positive LN (or additional positive LN in comparison to SLNB) | Recurrence rate |
Overall survival rate |
||
|---|---|---|---|---|---|---|---|---|---|
| Treatment arm | Control arm | Treatment arm | Control arm | ||||||
| NSABP-04 [4] | 1665 | 1971–1974 | Operable breast cancer | If cN0: a) total mastectomy b) total mastectomy + regional irradiation c) radical Mastectomy (control) If cN1: a) total mastectomy + regional irradiation b) radical mastectomy (control) |
n.A. | In cN0 10-year locoregional recurrence: a) 11.8% b) 4.6% In cN1 10-year locoregional recurrence:: 13.6% |
In cN0 10-year locoregional recurrence: 6.9% In cN1 10-year locoregional recurrence: 14.7% |
In cN0 10-year: a) 54% b) 59% In cN1 10-year: 39% |
In cN0 10-year: 58% In cN1 10-year: 38% |
| Louis-Sylvestre et al. [5] | 658 | 1982–1987 | cT1 and cT2≤3 cm, cN0 | Control: ALND Experimental: ART |
21% | 15-year local recurrence: 16.3% | 15-year local recurrence: 17.2% | 15-year: 75.5% | 15-year: 73.8% |
| NSABP-032 [7,8] | 5611 | 1999–2004 | cN0, any T | Control: SLNB + ALND Experimental: SLNB - if positive SLN - ALND - if negative SLN - no ALND |
38.6% | 8-year loco-regional recurrence: 3.1% | 8-year loco-regional recurrence: 3.1% | 5-year: 95.0% (95%CI 94.0–96.0) 8-year: 90.3% (95%CI 88.8–91.8) |
5-year: 96.4% (95%CI 95.6–97.2) 8-year: 91.8% (95%CI 90.4–93.3) |
| Z0011 [9] | 891 | 1999–2004 | cT1 and cT2 cN0 |
Control: SLNB with up to two metastases + ALND Experimental: SLNB with up to two metastases - no ALND |
27.3% | 10-year locoregional recurrence: 5.3% | 10-year locoregional recurrence: 6.2% | 10-year 86.3% (95%CI 82.2–89.5) | 10-year: 83.6% (95%CI 79.1–87.1) |
| AMAROS [10] | 1425 | 2001–2010 | cT1 and cT2 cN0 |
Control: SLNB with metastasis + ALND Experimental: SLNB with metastasis - ART |
33% | 10-year locoregional recurrence: 3.8% | 10-year locoregional recurrence: 3.4% | 10-year: 81.4% (95%CI 77.9–84.4) | 10-year: 84.6% (95%CI 81.5–87.1) |
| OTOASOR [11] | 474 | 2002–2009 | cT1 and cT2≤3 cm, cN0 | Control: SLNB with metastasis + ALND Experimental: SLNB with metastasis - RNI |
38.5% | 8-year axillary recurrence: 1.7% | 8-year axillary recurrence: 2.0% | 8-year: 84.8% | 8-year: 77.9% |
| IBCSG 23–01 [12] | 931 | 2001–2010 | cT1 and cT2, cN0 | Control: SLNB + ALND Experimental: SLNB - if macrometasis - ALND - if micrometastasis - no ALND |
13% in ALND group 3% in SLNB group with macrometastasis |
5-year locoregional recurrence: 2.8% 10-year locoregional recurrence: 6.6% |
5-year locoregional recurrence: 2.4% 10-year locoregional recurrence: 3.9% |
5-year: 97.5% (95%CI 95.8–99.1) 10-year: 90.8% (95%CI 87.9–93.8) |
5-year: 97.6% (95%CI 96.0–99.2) 10-year: 88.2% (95%CI 84.8–91.6) |
| AATRM [13] | 233 | 2001–2008 | cT1 and cT2≤3.5 cm, cN0 | Control: SLNB with micrometastasis + ALND Experimental: SLNB with micrometastasis - no ALND |
13.4% | 5-year disease recurrence: 2.5% | 5-year disease recurrence: 1% | n.A. | n.A. |
| SINODAR-ONE [14] | 889 | 2015–2020 | cT1 and cT2, cN0 | Control: SLNB with up to two macrometastases + ALND Experimental: SLNB with up to two macrometastases – no ALND |
44.0% | 5-year recurrence free survival: 95.6% 5-year locoregional recurrence: 1.6% |
5-year recurrence free survival: 96.4% 5-year locoregional recurrence: 0.9% |
5-year: 98.8% | 5-year: 98.9% |
LN – lymph node, SLN – sentinel lymph node, SLNB – sentinel lymph node biopsy; CI – confidence interval; RNI – Regional nodal irradiation; ART – axillary radiotherapy; n.A. – not available.