This study showed that survival was not improved in patients with invasive carcinoma when we performed complete ALND. The similar overall survival between the two groups provides evidence that ALND is unnecessary in patients with metastatic sentinel lymph nodes treated with conservative surgery and radiotherapy. This finding suggests that even in countries such as Brazil, where the overall survival in patients with breast cancer is lower than that in patients in developed nations,23 conservative surgical treatment of the axilla is possible. This result corroborates the data from the ACOSOG Z0011 trial.15
Patients who underwent SLND alone had a lower survival rate, although this was not statistically significant. This is probably because, in our study, patients in the SLND group received adjuvant chemotherapy less frequently (75% vs. 92.7% in SLND alone and ALND, respectively, p = 0.024, Table 1). Additionally, they were administered adjuvant chemotherapy because of comorbidities, and these data were not evaluated in the study.
The tendency towards reducing the use of intraoperative lymph node evaluation after the publication of the ACOSOG Z0011 trial was similar to that in other studies.6,7,28,29 Intraoperative assessment of the sentinel lymph node can be associated with a shorter average time of surgery,6 a reduction in perioperative costs,30,31 and a significant increase in the proportion of patients in whom complete dissection can be avoided.32 According to van der Noordaa et al.,33 intraoperative assessments of the sentinel lymph node should be performed only in patients with a restricted indication of lymph node dissection in the presence of metastasis in sentinel lymph node biopsy. Thus, the intraoperative assessment of the sentinel lymph node is not necessary for patients who meet the ACOSOG Z0011 criteria, and the surgical re-approach resulting from the definitive anatomopathological result of the axilla is rare (3.8%). This is an important finding in our study that can promote the practice of avoiding the intraoperative assessment of sentinel lymph nodes.
Locoregional recurrence was rare and similar between the groups. We believe that we had adequate follow-up time to evaluate recurrence. Long-term follow-up data from the NSABP trial19 showed that recurrence usually occurred early, at 14.8 months on average. In the ACOSOG Z0011 trial,18 recurrences occurred in 3.1 years, a bit shorter than our average follow-up time of 3.7 years.
The SLND group included women who were postmenopausal, with small tumors (pT1), positive hormone receptors, and small axillary involvement (35.7% with micrometastasis in the sentinel lymph node biopsy). These characteristics were similar to those of the same arm in the Z0011 trial.15,18 However, in the Z0011 study,15 the arm undergoing complete axillary dissection also had a high prevalence of micrometastases (37.5%), different from our study.
For patients with HER2 overexpression, triple-negative tumors and those aged below 50 years, using the ACOSOG Z0011 trial criteria can be discussed. Chung et al.34 reported no benefit of performing ALND in this subgroup. In our study, the groups were homogeneous in terms of these three variables. The underrepresentation of this group in the ACOSOG Z0011 trial may be due to the local demographic characteristics of patients with breast carcinoma. Nevertheless, it was assumed that the distribution of HER2 positive tumors was balanced between the two arms of the trial.
Several studies around the world have identified increasing acceptance of the Z0011 results and a change in clinical practice in relation to the standard treatment of axillary lymph nodes in patients with breast cancer.35–38.
A meta-analysis comparing SLND/radiotherapy only with ALND in early-stage breast cancer with limited sentinel node metastasis estimated that overall survival and disease-free survival were higher in the SLND group than in the ALND group and observed a greater axillary recurrence in the SLND/radiotherapy group. In conclusion, the omission of ALND in patients with one or two sentinel lymph nodes (SLNs) is indicated.39
Another meta-analysis of real-world cases evaluating the effects of SLND alone in patients with early-stage breast cancer and one or two positive SLN metastases in the post-Z011 era showed equivalent survival and recurrence outcomes between those undergoing SNLD alone or ALND, demonstrating that SLND alone was safe.40 However, this shift in clinical practice should not occur in patients with residual lymph node disease following neoadjuvant chemotherapy.41 All these studies included patients who were treated with systemic adjuvant therapy.
Complete ALND might be an overtreatment for many patients with capsular extravasation in the dissected sentinel lymph nodes. The Z0011 trial excluded patients with gross capsular extravasation and did not analyze the effect of microscopic capsular extravasation on recurrence or survival, making the management of these patients uncertain.15,18 The extension of capsular extravasation is directly associated with the burden of axillary disease.42 However, the rates of local, regional, or distant recurrence or mortality were similar between patients with and without capsular extravasation of ≤ 2 mm,43 and regional recurrence was rare and equal to that in patients without capsular extravasation even in the absence of nodal radiotherapy. Capsular extravasation is not the only reason for complete ALND.44 In our study, we identified five patients with capsular extravasation of ≤ 2 mm who were treated with SLND alone, avoiding the morbidity associated with complete axillary resection. However, these patients received regional radiotherapy at our hospital.
We acknowledge that translating the Z0011 results into clinical practice is complicated by the inconsistent use of radiotherapy fields in their study. In a prospective study of 793 patients with sentinel lymph node metastasis, using the ACOSOG Z0011 eligibility criteria resulted in the avoidance of ALND in 84% of patients, and the 5-year cumulative regional recurrence rate was 1%, which did not differ between radiotherapy fields. The authors concluded that even without the routine use of nodal radiotherapy, complete dissection could be avoided with excellent regional control.45 Hopefully, we will have answers about the real influence of radiotherapy in regional control with the results of the ongoing trials.46–49.
This was a retrospective study based on the medical records, which did not allow us to evaluate costs and surgical times after the change in the clinical approach in our hospital after the publication of the ACOSOG Z0011 study. Studies that evaluated cost reduction associated with the elimination of complete axillary dissection,30,31 did not consider the risk of surgical re-approach due to the presence of more than two sentinel lymph nodes compromised with macrometastasis or capsular extravasation. The cost of a second surgery remains to be evaluated. Even the ACOSOG Z0011 trial did not report the rate of surgical re-approach in the group subjected to SLND alone. The rate of surgical re-approach in this study was too low to answer this question. Nevertheless, this was the first study in our country to address the implementation of the findings of Z0011 and was important to encourage conservative surgical treatment of the axilla in our country and other developing countries, with the aim of disseminating this practice and benefiting patients.
The preliminary internal evaluation of the results of this study prompted major changes in our hospital’s clinical approach, with more conservative surgeries being performed and the elimination of ultrasonography, findings of which would often cause patients to undergo radical lymphadenectomy in the absence of sentinel lymph node biopsy results in the past.