Is completion axillary lymph node dissection necessary in patients who are underrepresented in the ACOSOG Z0011 trial?

Abstract

PurposeThe American College of Surgeons Oncology Group trial Z0011 demonstrated that axillary node dissection (ALND) can be omitted in patients managed with breast conserving surgery and 1 to 2 positive sentinel lymph nodes (SLNs) without adverse effects on locoregional recurrence or disease-free survival (DFS). We investigated patients with breast cancer for whom clinicopathologic features were underrepresented in the Z0011 trial and analyzed radiation therapy treatment patterns and clinical outcomes.Methods and materialsWe retrospectively reviewed records of patients who underwent a lumpectomy and SLN biopsy with positive SLNs but not an ALND and completed adjuvant radiation therapy. Eligible patients had T3 tumors, >2 positive SLNs, invasive lobular carcinoma, estrogen receptor negative status, extranodal extension, Nottingham Grade 3, or were age <50 years.ResultsWe identified 105 women treated between July 2011 and July 2016 with a median follow-up time of 48.5 months (Range, 11-83 months). There were 40 women with an extranodal extension (38.9%) and 42 women with grade 3 disease (40.0%). Nineteen patients received whole breast irradiation alone (18.1%) and 86 patients were treated with modified tangent fields including the superior axilla level I/II (81.9%). Thirty-three patients (31.4%) also received a 3rd supraclavicular, nodal-directed field. Among the 86 patients who received axillary nodal irradiation, nodal volume contouring was performed in 77 patients (89.5%). Fifty-one patients (48.6%) also received adjuvant chemotherapy. The overall rates of 4-year DFS and locoregional control (LRC) were 94.3% and 98.1%, respectively. Off all patients, 1 patient experienced an internal mammary nodal recurrence, another patient a contralateral breast tumor, and two patients distant metastases. There were no axillary or ipsilateral breast tumor recurrences.ConclusionsThis retrospective analysis of women who were underrepresented or excluded from the Z11 trial and underwent a lumpectomy and SLN biopsy with positive SLNs demonstrated comparable rates of LRC and DFS. The high rates of LRC and DFS suggest that completion ALND may be safely omitted in this patient population but larger data sets and longer follow-up times are needed to confirm this finding.

Management of the axilla in breast cancer: outcome analysis in a series of ductal versus lobular invasive cancers

“…Importantly, the percentage of patients with ILCs who had 3 or more metastatic lymph nodes at ALND, after a positive SLNB, was 27.50% versus only 11.48% of patients with IDCs (p = 0.04). These results seem to confirm the most recent literature showing a higher rate of residual nodal disease after positive SLNB in patients with ILC in comparison to IDC [19][20][21][22][23][24]. Adachi et al recently reported a very similar difference in the percentage of non-sentinel node metastases between ILCs and IDCs, with 68% of ILC patients having further metastatic deposits at ALND versus 46% of IDC patients [25].…”

External Validation of the SERC Trial Population: Comparison with the Multicenter French Cohort, the Swedish and SENOMIC Trial Populations for Breast Cancer Patients with Sentinel Node Micro-Metastasis

“…After the results of both the ACOSOG Z0011 and the IBCG 23-01 trials, it is considered safe to omit ALND in SLN positive patients. This had a major impact on clinical practice in breast cancer management and ALND omission was generalized even to the populations of patients under represented in these trials [ 8 , 9 , 13 ]. The use of restrictive inclusion/exclusion criteria in RCTs was identified as being one of the key factors limiting the external validity of trial findings [ 20 ].…”

“…Out of the three trials evaluating the role of axillary treatment in the case of axillary involvement, the ACOSOG-Z0011 trial included 35.1% patients with micro-metastases but in the analysis no differentiation was made between the patients with micro-metastases and patients with macro-metastases [ 13 ]. This issue was addressed in the IBCSG-23-01, where the recruited patients had only micro-metastases.…”

“…Both of the above cited trials induced important changes in clinical practice by eliminating the indications of ALND in patients presenting micro-metastases and patients presenting less than two SLN macro-metastases; however, the extrapolation of these results to the general population has been questioned. Both trials closed prematurely [ 11 ], did not achieve full patient accrual, presented lower numbers of events compared to what was expected, and the majority of patients included had favorable tumor prognostic features [ 4 , 12 , 13 , 14 , 15 , 16 ].…”

Do clinical trials truly mirror their target population? An external validity analysis of national register versus trial data from the Swedish prospective SENOMIC trial on sentinel node micrometastases in breast cancer

“…However, the generalizability of results has been questioned [13][14][15][16]. Both ACOSOG Z0011 and IBCSG 23-01 closed early due to slow accrual and low event rates, and the majority of included patients had favorable prognostic tumor characteristics [17,18].…”