Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases.

BACKGROUND: Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups. METHODS: We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44. RESULTS: Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy-only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy-only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin. CONCLUSIONS: The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).

The Potential Impact of AMAROS on the Management of the Axilla in Patients with Clinical T1-2N0 Breast Cancer Undergoing Primary Total Mastectomy.

BACKGROUND: Recent trials have demonstrated that axillary observation or axillary radiation therapy (AxRT) is equivalent to axillary node dissection (ALND) for patients with one or two positive sentinel lymph nodes (SLNs). These strategies have been widely adopted for patients having breast conservation. This report demonstrates the potential impact of the AMAROS trial on axillary therapy in a retrospective cohort of mastectomy patients. METHODS: Patients undergoing primary mastectomy for cT1-2N0 breast cancer who had one or two positive SLNs were identified from institutional databases (2005-2015). Locoregional management strategies were evaluated, and variables predictive of the use of postmastectomy radiation therapy (PMRT) were identified. RESULTS: Among 2594 mastectomies, 193 (7%) met the AMAROS eligibility criteria. The median patient age was 50 years (range 22-83 years). Locoregional treatment consisted of ALND + PMRT for 102 patients (53%), ALND alone for 66 patients (34%), PMRT alone for 11 patients (6%), and observation for 14 patients (7%). Overall, 59 ALND patients (35%) had additional positive nodes. In the multivariate analysis, age younger than 50 years (odds ratio [OR] 3.55; 95% confidence interval [CI] 1.57-8.45), lymphovascular invasion (LVI) (OR 5.78; 95% CI 2.53-4.78), macrometastases (OR 3.99; 95% CI 1.54-10.97), and extracapsular extension (OR 11.66; 95% CI 2.55-88.34) were associated with receipt of PMRT. CONCLUSION: In this cohort of AMAROS-eligible patients, 168 (87%) underwent ALND, 102 (61%) of whom also received PMRT, suggesting that AxRT could have been used instead of ALND for a significant number of patients. Preoperative factors associated with the receipt of PMRT, such as young age and LVI, may be useful for defining a multidisciplinary decision-making framework for axillary management in this population.