Axillary Lymph Node Management

ALMANAC, a randomized trial of 1,031 women compared SLN biopsy followed by ALND when the SLN was positive with ALND in all patients.[29][Level of evidence A3]

ALMANAC, a randomized trial of 1,031 women compared SLN biopsy followed by ALND when the SLN was positive with ALND in all patients.[29][Level of evidence A3]

Quality of life at 1 year (as assessed by the frequency of patients experiencing a clinically significant deterioration in the Trial Outcome Index of the Functional Assessment of Cancer Therapy-Breast scale) was superior in the SLN biopsy group (23% deteriorating in the SLN biopsy group vs. 35% in the ALND group; P = .001). Arm function was also better in the SLN group.

The National Surgical Adjuvant Breast and Bowel Project’s (NSABP-B-32 [NCT00003830]) multicenter, phase III trial randomly assigned women (N = 5,611) to undergo either SLN plus ALND or SLN resection alone. ALND was only performed if the SLNs were positive.[30][Level of evidence A1]

The National Surgical Adjuvant Breast and Bowel Project’s (NSABP-B-32 [NCT00003830]) multicenter, phase III trial randomly assigned women (N = 5,611) to undergo either SLN plus ALND or SLN resection alone. ALND was only performed if the SLNs were positive.[30][Level of evidence A1]

The study showed no detectable difference in overall survival (OS), disease-free survival (DFS), and regional control. The OS rate was 91.8% for SLN plus ALND versus 90.3% for SLN resection alone (P = .12).

ACOSOG Z0011 (Alliance, NCT00003855), a phase III, noninferiority, multicenter, randomized clinical trial, evaluated whether ALND is required after a positive SLN biopsy. Women were randomly assigned to undergo ALND or no further axillary treatment. Patients had clinical T1 or T2 invasive breast cancer without palpable adenopathy and one to two SLNs containing metastases identified by frozen section. All patients underwent lumpectomy, tangential whole-breast radiation therapy, and appropriate systemic therapy. OS was the primary end point, and DFS was the secondary end point. Because of enrollment challenges, a total of 891 women out of a target enrollment of 1,900 women were randomly assigned to one of the two treatment arms.[Level of evidence A1]

ACOSOG Z0011 (Alliance, NCT00003855), a phase III, noninferiority, multicenter, randomized clinical trial, evaluated whether ALND is required after a positive SLN biopsy. Women were randomly assigned to undergo ALND or no further axillary treatment. Patients had clinical T1 or T2 invasive breast cancer without palpable adenopathy and one to two SLNs containing metastases identified by frozen section. All patients underwent lumpectomy, tangential whole-breast radiation therapy, and appropriate systemic therapy. OS was the primary end point, and DFS was the secondary end point. Because of enrollment challenges, a total of 891 women out of a target enrollment of 1,900 women were randomly assigned to one of the two treatment arms.[Level of evidence A1]

At a median follow-up of 6.3 years, the 5-year OS rate was 91.8% (95% confidence interval [CI], 89.1%–94.5%) with ALND and 92.5% (95% CI, 90.0%–95.1%) with SLN biopsy alone.

ACOSOG Z0011 (Alliance, NCT00003855), a phase III, noninferiority, multicenter, randomized clinical trial, evaluated whether ALND is required after a positive SLN biopsy. Women were randomly assigned to undergo ALND or no further axillary treatment. Patients had clinical T1 or T2 invasive breast cancer without palpable adenopathy and one to two SLNs containing metastases identified by frozen section. All patients underwent lumpectomy, tangential whole-breast radiation therapy, and appropriate systemic therapy. OS was the primary end point, and DFS was the secondary end point. Because of enrollment challenges, a total of 891 women out of a target enrollment of 1,900 women were randomly assigned to one of the two treatment arms.[Level of evidence A1]

Detailed analysis of the radiation field design found that 15% of patients also received treatment to the supraclavicular region (in addition to standard tangents). Of those with detailed radiation records available for review, 43 patients (18.9%) received regional nodal radiation therapy.[31]

ACOSOG Z0011 (Alliance, NCT00003855), a phase III, noninferiority, multicenter, randomized clinical trial, evaluated whether ALND is required after a positive SLN biopsy. Women were randomly assigned to undergo ALND or no further axillary treatment. Patients had clinical T1 or T2 invasive breast cancer without palpable adenopathy and one to two SLNs containing metastases identified by frozen section. All patients underwent lumpectomy, tangential whole-breast radiation therapy, and appropriate systemic therapy. OS was the primary end point, and DFS was the secondary end point. Because of enrollment challenges, a total of 891 women out of a target enrollment of 1,900 women were randomly assigned to one of the two treatment arms.[Level of evidence A1]

The 5-year DFS rate was 82.2% (95% CI, 78.3%–86.3%) with ALND and 83.9% (95% CI, 80.2%–87.9%) with SLN biopsy alone.

In a similarly designed trial (IBCSG 23-01), 929 women with breast tumors smaller than 5 cm and SLN involvement smaller than 2 mm were randomly assigned to ALND or no ALND.[32][Level of evidence A1]

In a similarly designed trial (IBCSG 23-01), 929 women with breast tumors smaller than 5 cm and SLN involvement smaller than 2 mm were randomly assigned to ALND or no ALND.[32][Level of evidence A1]

Patients without axillary dissection had fewer DFS events (hazard ratio [HR], 0.78; 95% CI, 0.55–1.11).

In a similarly designed trial (IBCSG 23-01), 929 women with breast tumors smaller than 5 cm and SLN involvement smaller than 2 mm were randomly assigned to ALND or no ALND.[32][Level of evidence A1]

No difference in OS was observed.

The AMAROS trial (NCT00014612) studied ALND and axillary radiation therapy after identification of a positive SLN.[33][Level of evidence A1]

The AMAROS trial (NCT00014612) studied ALND and axillary radiation therapy after identification of a positive SLN.[33][Level of evidence A1]

ALND and axillary radiation therapy provided excellent and comparable axillary control for patients with T1 or T2 primary breast cancer and no palpable lymphadenopathy who underwent breast-conserving therapy or mastectomy.

The AMAROS trial (NCT00014612) studied ALND and axillary radiation therapy after identification of a positive SLN.[33][Level of evidence A1]

The use of axillary radiation therapy was also associated with significantly less morbidity.

The SOUND trial (NCT02167490), a multicenter, noninferiority, randomized clinical trial, evaluated omitting SLN biopsy in women with invasive breast cancer. Patients were of any age, had tumors smaller than 2 cm, had negative preoperative axillary ultrasonography, and planned to receive breast-conserving surgery and adjuvant radiation therapy. A total of 1,493 women were randomly assigned to undergo SLN biopsy or no axillary surgery. The median follow-up was 5.7 years.[34][Level of evidence A1]

The SOUND trial (NCT02167490), a multicenter, noninferiority, randomized clinical trial, evaluated omitting SLN biopsy in women with invasive breast cancer. Patients were of any age, had tumors smaller than 2 cm, had negative preoperative axillary ultrasonography, and planned to receive breast-conserving surgery and adjuvant radiation therapy. A total of 1,493 women were randomly assigned to undergo SLN biopsy or no axillary surgery. The median follow-up was 5.7 years.[34][Level of evidence A1]

The 5-year distant DFS rate was 97.7% in the SLN biopsy group and 98.0% in the no-surgery group (log-rank P = .67; HR, 0.84; 90% CI, 0.45–1.54; noninferiority P = .02).

The SOUND trial (NCT02167490), a multicenter, noninferiority, randomized clinical trial, evaluated omitting SLN biopsy in women with invasive breast cancer. Patients were of any age, had tumors smaller than 2 cm, had negative preoperative axillary ultrasonography, and planned to receive breast-conserving surgery and adjuvant radiation therapy. A total of 1,493 women were randomly assigned to undergo SLN biopsy or no axillary surgery. The median follow-up was 5.7 years.[34][Level of evidence A1]

A total of 12 locoregional relapses (1.7%), 13 distant metastases (1.8%), and 21 deaths (3.0%) were observed in the SLN biopsy group, compared with 11 locoregional relapses (1.6%), 14 distant metastases (2.0%), and 18 deaths (2.6%) in the no-surgery group.

The multicenter, noninferiority, randomized INSEMA trial (NCT02466737) evaluated omitting SLN biopsy in 5,502 women with clinically node-negative invasive breast cancer. Tumors had to be smaller than 5 cm, and most patients had T1 disease and ER-positive tumors. Patients were scheduled to undergo breast-conserving surgery and whole-breast radiation therapy. Patients were randomly assigned in a 1:4 ratio to undergo no axillary surgery or SLN biopsy. The median follow-up was 6 years.[35][Level of evidence A1]

The multicenter, noninferiority, randomized INSEMA trial (NCT02466737) evaluated omitting SLN biopsy in 5,502 women with clinically node-negative invasive breast cancer. Tumors had to be smaller than 5 cm, and most patients had T1 disease and ER-positive tumors. Patients were scheduled to undergo breast-conserving surgery and whole-breast radiation therapy. Patients were randomly assigned in a 1:4 ratio to undergo no axillary surgery or SLN biopsy. The median follow-up was 6 years.[35][Level of evidence A1]

The 5-year invasive DFS rate was 91.9% in the no-surgery group and 91.7% in the SLN biopsy group (HR, 0.91; 95% CI, 0.73–1.14), which was below the prespecified noninferiority margin.

The multicenter, noninferiority, randomized INSEMA trial (NCT02466737) evaluated omitting SLN biopsy in 5,502 women with clinically node-negative invasive breast cancer. Tumors had to be smaller than 5 cm, and most patients had T1 disease and ER-positive tumors. Patients were scheduled to undergo breast-conserving surgery and whole-breast radiation therapy. Patients were randomly assigned in a 1:4 ratio to undergo no axillary surgery or SLN biopsy. The median follow-up was 6 years.[35][Level of evidence A1]

Patients in the no-surgery group had a lower incidence of lymphedema, greater arm mobility, and less pain with movement of the arm or shoulder than patients who underwent SLN biopsy.