Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study

Abstract

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).

The Clinical Relevance of Target Lymph Node Biopsy after Primary Systemic Therapy in Initially Node-Positive Breast Cancer Patients

“…Results from the Dutch MINIMAX study (NCT04486495) are expected in 2027 [ 30 ]. The 5-year invasive DFS data and axillary recurrence rate from the European AXSANA study (NCT04373655), depending on the type of axillary surgery, will be available in 2030 [ 1 ].…”

“…Currently, the optimal axillary surgical approach for breast cancer patients with initial node-positive disease and conversion to clinically node-negative status after primary systemic therapy (PST) is unclear. The various international guidelines provide very different recommendations in this issue [ 1 ]. On the one hand, depending on tumor biology, 40–74% of these patients achieve a pathologically negative nodal status by PST [ 2 , 3 , 4 ], and therefore are candidates for less radical axillary surgery such as sentinel lymph node biopsy (SLNB), which is less likely to lead to complications such as pain, shoulder dysfunction, paraesthesia, or lymphedema compared with complete axillary lymph node dissection (ALND) [ 5 , 6 ].…”

Update Breast Cancer 2021 Part 3 – Current Developments in the Treatment of Early Breast Cancer: Review and Assessment of Specialised Treatment Scenarios by an International Expert Panel

“…Both the study by Caudle et al [39] and the German SENTA study [40] attest to a false negative rate respectively of 1.4 % and 4.3 % for TAD. As survival data on TAD are still pending, participation in the ongoing AXSANA trial is recommended [41].…”

“…Sowohl die Studie von Caudle et al 39 als auch die deutsche SENTA-Studie 40 attestieren der TAD eine Falsch-negativ-Rate von 1,4% respektive 4,3%. Da Überlebensdaten zur TAD noch ausstehen, ist die Teilnahme an der laufenden AXSANA-Studie zu empfehlen 41 .…”

Superparamagnetic Iron Oxide for Identifying Sentinel Lymph Node in Breast Cancer after Neoadjuvant Chemotherapy: Feasibility Study

“…Sentinel lymph node biopsy (SLNB) is a well-established procedure for staging clinically node-negative early breast cancer (BC), although the optimal surgical management of the axilla has been controversially discussed over the last two decades [ 1 ]. Due to its minimally invasive approach and low morbidity, SLNB established a new milestone replacing axillary lymph node dissection (ALND) [ 2 , 3 ].…”