Ongoing clinical trials on axillary management.

Abstract

Introduction: Within the last 50 years the management of patients with breast cancer has changed dramatically with a significant de-escalation of the role and magnitude of surgery, both for the management of the primary tumor and for the management of the axilla. In the management of the axilla of patients with early stage breast cancer (EBC) and clinically uninvolved axilla (cN0), axillary lymph node dissection (ALND) was gradually replaced by sentinel lymph node biopsy (SLNB) saving more than 60-70% of patients from an unnecessary dissection. Further studies confirmed that isolated tumor cells or micrometastases found on the SLN had no further benefit from ALND sparing even more patients from an unnecessary ALND. Eventually, the Z0011 and other studies showed that even patients with 1-2 positive SLN can be spared from ALND provided they fulfill certain criteria. Still though there were many flaws in these studies and further research was necessary to generalize the results of these studies to a wider target group. Meanwhile, there is a clear view that many low risk patients if they have their axilla evaluated via US and are not found to have suspicious nodes, it is highly unlikely to have involved axilla. This let to studies evaluating the non-surgical management of the axilla. Finally, in the post neoadjuvant setting 3 randomized controlled trials showed that under certain circumstances SLNB can be done after the NAC even in patients who initially had involved axilla and was converted to clinically uninvolved (cN1→cN0).

Evidence acquisition: PubMed, Medline, the Cochrane Library Controlled Trials Register as well as National Institutes of Health ClinicalTrials.Gov database have been consulted up to May 2020.

Evidence synthesis: We studied and described the ongoing trials on patients not undergoing neoadjuvant chemotherapy and we discussed the eligibility criteria, the comparison arms and the expected outcomes. We further examined the ongoing trials on patients undergoing neoadjuvant chemotherapy in the same manner.

Conclusions: Although we have covered a long way in the journey of eliminating axillary surgery, there are still lots of questions to be answered and trials to be conducted. We anticipate the results of the ongoing trials to provide the necessary evidence to safely de-escalate more the axillary surgery, both in the non-neoadjuvant as well as in the neoadjuvant setting, hoping that in the not so far future the axillary surgery will eventually perish.