ALND Necessity Questioned For Breast Cancer Extranodal Extension

Extranodal extension in breast cancer patients is significantly linked to axillary nodal burden but not survival or recurrence

medwireNews: Microscopic extranodal extension (ENE) on sentinel lymph node biopsy (SLNB) predicts a greater axillary nodal burden and the likelihood of N2 disease in early breast cancer patients, suggests research published in JAMA Surgery.

However, there was no significant difference in the likelihood of survival or recurrence between patients with and without ENE, regardless of whether it was 2 mm or below, or larger.

Maheswari Senthil and co-authors, from the Loma Linda University School of Medicine in California, USA, explain that, following results from the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, the standard of care changed from completion axillary lymph node dissection (ALND) for all patients with one or more positive SLN, to SLN dissection alone or alongside radiotherapy for those with T1N0 or T2N0 disease.

However, due to a lack of information on disease risk in T1N0 and T2N0 patients who are found to have ENE, ALND has continued in these subgroups.

In light of the current study, the researchers now“recommend that reporting of ENE size detected on [SLNB] should be incorporated into the College of American Pathologists reporting guidelines”, and suggest further analysis of data from both the Z0011 trial and the AMAROS (After Mapping of the Axilla: Radiotherapy or Surgery?) trial to clarify outcomes for patients with microscopic ENE.

“Validation of these findings with prospective data would help inform treatment decisions in this group of patients in an era when the Z0011 and AMAROS results are being used to better define groups of patients who can forgo further axillary surgery or be treated with [axillary radiotherapy] as an alternative to ALND”, they write.

The current study reviewed medical records for 208 patients who met the ACOSOG Z0011 trial criteria as requiring ALND, defined as T1N0 or T2N0 breast cancer with one or two positive SLNs.

On ALND, the majority (71.6%) of patients had no ENE, 10.1% had ENE of 2 mm or less and 18.3% had ENE greater than 2 mm.

The average number of positive lymph nodes was significantly lower in patients with no ENE than in those with ENE of up to 2 mm or more than 2 mm, at 1.72 versus 3.22 and 4.26, respectively. The average number of non-SLN metastases was also significantly smaller in patients without ENE than the two groups with ENE, at 0.48 versus 1.91 and 2.95, respectively.

After considering tumour size, number of positive LNs and adjuvant therapy, however, the presence of ENE 2 mm or below was independent of mortality risk, whereas three or more positive lymph nodes (hazard ratio [HR]=3.98) and receipt of hormone therapy (HR=0.41) were significant modifiers of survival.

Similarly, in multivariate analysis, the presence of ENE greater than 2 mm did not significantly alter survival, whereas increasing tumour size (HR=1.85) and more than three positive LNs (HR=3.85) significantly predicted an increased risk of mortality. Hormone therapy again was found to be protective, with a HR of 0.36.

There was no significant difference in the rate of local, nodal or distant recurrence between patients with no ENE and those with ENE of 2 mm or less. And although there was a trend towards a higher rate of distance recurrence with ENE larger than 2 mm compared with no ENE, at 10.5% versus 2.7%, this difference did not reach significance.

Kimberly Stone and Amanda Wheeler, from Stanford University in Palo Alto, California, USA, discuss the study in an invited commentary and note that the impact of EME and nodal tumour burden on the risk of regional recurrence in patients treated with ALND and multimodal therapy is unknown.

“It is clear that the risk of nodal recurrence is substantially lower than the incidence of disease left behind in the nodes”, they observe.

“As we continue to tailor our treatment to the biology of the tumor and its molecular footprint, we have improved on the disease-free and overall survival with a similar improvement in locoregional control”, the commentators write.

“The recognition of the significance of ENE as a predictor of a heavy nodal tumor burden may be a useful window into the aggressive nature of the biology of the tumor.”


Choi AH, Blount S, Perez MN, et al. Size of extranodal extension on sentinel lymph node dissection in the American College of Surgeons Oncology Group Z0011 trial era. JAMA Surg 2015; Advance online publication 2 September.doi:10.1001/jamasurg.2015.1687

Stone K, Wheeler AJ. The biology behind the American College of Surgeons Oncology Group Z0011 trial. JAMA Surg 2015; Advance online publication 2 September.doi:10.1001/jamasurg.2015.1716

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