Reviewed by Dr. Jasmine Singh
Giuliano AE et al. JAMA. 2017 Sep; 318(10): 918-926
The American College of Surgeons Oncology Group Z0011 (Z0011) trial previously established the safety of omitting routine axillary lymph node dissection (ALND) in women with early-stage breast cancer (T1 or T2), no palpable axillary adenopathy, and one or two metastatic sentinel lymph nodes. This study provided extended 10-year surveillance of this patient population.
856 patients across multiple medical centers were included in the trial and enrolled from 1999 to 2004, with 446 in the SLND (sentinel lymph node dissection) alone group and 445 in the ALND group. Estrogen and progesterone receptor status of patients in ALND and SLND groups is provided in table 1. The 10-year overall survival was 86.3% in the SLND group and 83.6% in the ALND group (HR, 0.85 [1-sided 95% CI, 0-1.16]; non-inferiority P = .02). The 10-year disease-free survival was 80.2% in the SLND alone group and 78.2% in the ALND group (HR, 0.85 [95%CI, 0.62-1.17]; P = .32). Non-inferiority between the two groups remained present regardless of hormone receptor positivity status. Between years 5 and 10, there was 1 regional recurrence in the SLND but none in the ALND group. However, the 10-year regional recurrence rate did not have a significant difference between the groups.
Before the initial Z0011 trial was published, there was a general consensus that ALND is necessary to control regional breast cancer in patients with metastases to sentinel lymph nodes. ALND is not without morbidity. Adverse effects include, but are not limited to, wound infections, lymphedema, and paresthesias. With the advent of SLND we thus see an example of de-escalation of care leading to a non-inferior effect on survival and likely also improving quality of life for this patient population.
The initial study had a median follow up of 6.3 years. The majority of these patients had hormone receptor positive tumors which have high risk of long-term recurrence, including after 5 years of initial presentation. One major criticism of the original study was thus the lack of late follow-up, which may detect future disease recurrence and death. The 10-year surveillance outcomes support previous conclusions that ALND is not necessary for survival benefit but instead a breast conserving approach with SLND is appropriate in patients with positive sentinel lymph nodes. These conclusions apply even to women in late recurring, hormone receptor positive tumors.
One major limitation of the study is the significant amount of women lost to follow-up (166/856, 19.4%). The data for these patients was censored and not included to determine survival outcomes. However, if a large proportion of these women were located and found to have an outcome of locoregional or systemic recurrence, or even death, it could skew outcomes. It should also be recognized that during surgical treatment of patients, a larger number of micrometastases in sentinel lymph nodes were found in the SLND group as opposed to the ALND group (44.8% vs 37.5). Further long-term surveillance is needed to determine how this would affect survival and outcomes.