AXillary Surgery After NeoAdjuvant Treatment (AXSANA)

A Prospective Multicenter Cohort Study to Evaluate Different Surgical Methods of Axillary Staging (Sentinel Lymph Node Biopsy, Targeted Axillary Dissection, Axillary Dissection) in Clinically Node-positive Breast Cancer Patients Treated With Neoadjuvant Chemotherapy

The optimal surgical axillary staging technique in patients who convert from the clinically positive to clinically negative lymph node status under neoadjuvant therapy (cN+ → ycN0) remains to be clarified. Different strategies (axillary lymph node dissection, sentinel node biopsy, targeted axillary dissection) are currently used in different countries. A prospective analysis comparing these techniques regarding feasibility, safety, morbidity and surgical effort is urgently needed. Due to high complexity and discordant recommendations, a randomized trial comparing different techniques is hardly feasible. Therefore, the EUBREAST study group decided to initiate a prospective cohort study as an international project that aims at comparatively evaluating data on axillary staging after neoadjuvant therapy.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer

Detailed Description

For many decades, axillary lymph node dissection (ALND) has been considered standard of care in breast cancer (BC) patients. The procedure aimed at assessing the pN status to guide adjuvant therapy decisions as well as ensuring adequate locoregional control. However, ALND is associated with high morbidity and may therefore lead to reduced quality of life in BC patients.

In women undergoing primary surgery, ALND as a staging tool has been replaced by the less invasive sentinel lymph node biopsy (SLNB) without compromising the disease-free or overall survival (DFS, OS). Since then, the therapeutic benefit of ALND in patients with clinically occult metastasis in the sentinel lymph node (SLN) has been challenged as well. According to the current national and international guidelines (e.g. ESMO, NCCN, German S3 guideline and AGO recommendations) completion ALND can be safely omitted in selected patients with 1-2 positive sentinel lymph nodes.

The feasibility and safety of the SLNB after neoadjuvant chemotherapy (NACT) has been controversially discussed, particularly regarding women who initially presented with positive lymph nodes (cN+) and converted to ycN0 following NACT. In these patients, two large prospective multicenter trials reported a false-negative rate (FNR) of 12 and 14%, respectively, thus exceeding the generally accepted (albeit arbitrarily chosen) cutoff of 10%. The clinical relevance of an FNR > 10% and its impact on oncological endpoints (DFS, OS) remains unclear. For this reason, numerous national guidelines still recommend ALND in these patients.

Possible ways to further reduce the FNR in cN+ patients have been extensively discussed in the recent years. In 2016, a novel surgical approach (TAD = targeted axillary dissection) has been reported that consists of inserting a marking (e.g. a clip or a radioactive tracer) into the metastatic lymph node before NACT. In patients in whom the marked lymph node (target lymph node = TLN) and the sentinel node had been successfully removed, the FNR was as low as 1.4%. These retrospectively analyzed data from a prospective register support the hypothesis that TAD can improve the relatively low success rates of SLNB and reduce the long-term morbidity of patients undergoing axillary surgery in the neoadjuvant setting.

Several issues regarding currently used axillary staging techniques remain yet to be clarified. Based on the unclear evidence, the guideline recommendations for the cN+ → ycN0 patients differ strongly. The current ESMO guidelines state that (1) SLNB may be carried out in selected cases, and, if negative, further axillary surgery may be avoided and (2) the FNR of SLNB alone can be improved by marking the biopsied positive node(s) to verify the removal. In Germany, the S3 guideline (last version: 2020) recommends ALND in patients with initial nodal involvement. In contrast, the German Working Group Gynecological Oncology (AGO) changed their recommendations in 2019 and endorsed TAD as a technique of choice for this patient subgroup. In several European countries (Sweden, Norway, Finland) ALND is still considered standard of care for these patients. In others, such as Italy, most patients receive SLNB alone without marking and removing the target lymph node. In the current NCCN guidelines the TAD is considered an optional technique. A prospective analysis comparing different techniques regarding feasibility, safety, morbidity and surgical effort is urgently needed. Due to high complexity and discordant recommendations, a randomized trial comparing different techniques is hardly feasible and therefore would not clarify currently open issues within a reasonable timeframe.

Based on the lack of sufficient evidence and discrepancies between different national and institutional standards, the EUBREAST study group (www.eubreast.com) decided to initiate a prospective cohort study as an international project that aims at comparatively evaluating data on axillary staging after NACT.

• Study Type: Observational
• Enrollment (Estimated): 3000

Contacts and Locations

• Study Contact: Name: Thorsten Kühn, Prof.; Phone Number: +4971131033051 +49711 3103-3051; Email: info@eubreast.com
• Study Contact Backup: Name: Maggie Banys-Paluchowski, PD Dr.; Email: m.banys@outlook.com

Study Locations

• Germany
  • Esslingen, Germany
    • Recruiting
    • Klinikum Esslingen
    • Contact: Thorsten Kühn, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Breast cancer patients with lymph node metastasis undergoing neoadjuvat chemotherapy.

Description

Inclusion Criteria:

• Signed informed consent form
• Primary invasive breast cancer (confirmed by core biopsy)
• cN+
• cT1-4c
• Scheduled for neoadjuvant systemic therapy
• Female / male patients ≥ 18 years old

Exclusion criteria

• Distant metastasis
• Recurrent breast cancer
• Inflammatory breast cancer
• Extramammary breast cancer
• Supraclavicular lymph node metastasis
• Pregnancy
• Less than 4 cycles of NACT administered
• Patients not suitable for surgical treatment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive disease-free survival (iDFS)	iDFS is defined as time from surgery to the first clinical, radiological or histological diagnosis of invasive relapse	5 years
Axillary recurrence rate	Axillary recurrence is defined as radiological and/or histological diagnosis of tumor recurrence in the axilla	3 years
Health-related quality of life	Health-related QoL will be assessed with the EORTC Quality of life questionnaires	5 years
Arm morbidity	Arm morbidity will be assessed with the Lymph IFC questionnaire	5 years

Collaborators and Investigators

• Sponsor: European Breast Cancer Reseach Association of Surgical Trialists
• Collaborators: German Breast Group; North Eastern German Society of Gynaecological Oncology; AGO-B; AWOgyn; Claudia von Schilling Foundation for Breast Cancer Research; Ehmann-Stiftung Savognin
• Investigators: Study Chair: Thorsten Kühn, Prof., EUROPEAN BREAST CANCER RESEARCH ASSOCIATION OF SURGICAL TRIALISTS

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2020
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: April 29, 2020
• First Submitted That Met QC Criteria: May 1, 2020
• First Posted (Actual): May 4, 2020

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; neoadjuvant chemotherapy; sentinel node biopsy; axillary lymph node dissection; targeted axillary dissection; target lymph node
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: EUBREAST 3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No