Axillary lymph node dissection not supported in study of invasive breast cancer with sentinel node metastasis
For more than 100 years, the standard of care for breast cancer with metastases to the sentinel lymph nodes has been axillary lymph node dissection (ALND), which is associated with numerous complications as well as reduced quality of life. We now understand that breast cancer biology plays a major role in recurrence. This has opened the door to new surgical approaches in managing the disease, including sentinel lymph node dissection (SLND).
In 2005, a randomized clinical trial from the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) reported that the overall survival (OS) in patients who had SLND alone was no worse than patients with ALND (median follow-up of 6.3 years).1 It also showed no statistically significant difference in disease-free survival (DFS) between the groups; nodal recurrence occurred in less than 1% of patients in both groups.
Although the study was criticized for the short follow-up, the results dramatically changed the surgical approach to the axilla for early-stage, node-negative breast cancer. After the results were published, use of ALND decreased from 71% to 17% in one 12-hospital network; similar decreases were noted in other hospitals.2
Recently, a group of investigators felt that longer follow-up was needed, as estrogen receptor-positive tumors often recur later in the course of the disease. The objective of their study was to determine whether the 10-year OS of patients with sentinel lymph node metastases treated with breast-conserving therapy and SLND alone is noninferior to axillary dissection.2
The authors reported that 10-year OS as well as 10-year DFS was similar in both groups.
“These findings do not support routine use of axillary lymph node dissection in this patient population based on 10-year outcomes,” concluded Armando Giuliano, MD, of the Department of Surgery at Cedars-Sinai Medical Center in Los Angeles, and his colleagues. They also cautioned that the conclusions apply only to patients meeting the eligibility criteria of this study, and should not be extrapolated to other breast cancer patients.
The ACOSOG is now part of the Alliance for Clinical Trials in Oncology (Alliance). In the original study, patients with 1 or 2 sentinel nodes with metastases were randomized to SLND alone (no further axillary-specific treatment) or ALND. Follow-up was planned for 10 years.
The ACOSOG Z0011 phase 3 randomized clinical trial enrolled 891 women (436 SLND alone, 420 ALND) at 115 sites with clinical T1 or T2 invasive breast cancer, no palpable axillary adenopathy, and one or two sentinel lymph nodes containing metastases. All patients had planned lumpectomy, tangential whole-breast irradiation, and adjuvant systemic therapy; third-field radiation was not allowed.
Patients were enrolled from May 1999 to December 2004, with the last follow-up occurring in September 2015. The primary outcome was OS as a measure of noninferiority, and the secondary outcome was DFS. An exploratory analysis was conducted to determine the effect of treatment on OS for patients with hormone receptor-positive tumors.
Demographic and disease characteristics at baseline were similar between the groups. Fewer lymph nodes were removed in the SLND group (median of 2) than in the ALND group (median of 17). The median total number of nodes containing metastases in both groups was one. At a median follow-up of 9.3 years there were 110 deaths (51 in SLND alone group, 59 in ALND group).
After 10 years of follow-up, OS was similar in both groups (86.3% in the SLND alone and 83.6% in the ALND). In addition, 10-year DFS was also similar in both groups (80.2% in the SLND alone and 78.2% in the ALND). In a multivariable analysis of OS, type of treatment was not associated with OS.
The exploratory analysis of the effect of treatment and hormone receptor status showed that the type of surgery had no significant effect on OS with respect to hormone receptor status.
The authors noted that the study has some limitations. Not all biological subtypes are represented in large numbers, and the study did not reach the predetermined sample size (1900 participants, 500 deaths) due to low accrual and low event rate. Some patients also had irradiation protocol variations (the distribution was similar in both groups).
The investigators concluded that the results of ten years of follow-up confirm that in invasive primary breast cancer with no palpable axillary adenopathy and metastases in one or two sentinel lymph nodes, SLND alone was noninferior to OS for those treated with ALND.
To read more about this study, click here.
References:
1. Lucci A, et al. J Clin Oncol. 2007;25(24):3657-3663.
2. Giuliano AE, et al. JAMA. 2017;318(10):918-926.