No Axillary sUrgical Treatment In Clinically Lymph Node Negative Patients After UltraSonography

[Background] Skipping ALND, the follow-up treatment in SN-positive patients, has non-inferior oncological outcomes compared to SLNB-only group, given that there is no severe SN metastases.

Axillary ultrasound can effectively exclude high nodal burden, showing 95% NPV in a systematic review.

SLNB has morbidity including lymphedema, limited range of motion, pain, and other post-surgical complications, eventually leading to reduced quality of life.

Considering improvement of imaging modalities and adjuvant care, survival outcome of SLNB must be re-evaluated. Especially research reflective of the regional specificities of Korea and Asia-Pacific is needed.

[Study design] Prospective, Multicenter, RCT.

[Statistical considerations] According to Z0011 trial, 5yr DFS in eligible patients is expected to be 86%, which is between previous data of 88.6% in cT1,2 and SN-negative patients4, and 83.9% in cT1,2 and 1-2 SN-positive patients.

Non-inferiority margin is set at 5%. With 5% significance level and 80% power, 780 patients are needed in each group. Assuming a 10% drop out rate, 1734 patients need to be recruited.

[Screening and Randomization] Participants undergo screening tests that assess eligibility according to inclusion/exclusion criteria.

In order to identify axillary lymph node metastases, axillary ultrasound is first performed by radiologists. Patients showing normal features are enrolled, while for conditionally normal patients, with only 1 suspicion of low nodal burden, axillary lymph node biopsy should be performed. Suspicious patients are excluded under following conditions: patients with 1 or more suspicion of high nodal burden, 2 or more suspicion of low nodal burden, or T2 invasive lobular carcinoma patients with 1 or more low nodal burden. The severity of nodal burden is defined through the criteria.

Patients who underwent radiological axillary staging are randomly assigned (1:1) to the study arm and the control arm before surgical care. Stratification is done based on trial centers and tumor sizes.

[Post-surgical care] All patients are planned to receive ipsilateral whole breast radiation. Patients randomized to non-SLNB arm are recommended to follow high tangential radiotherapy protocol, in which upper margin of radiation field includes axillary level I and II or lies within 2CM from humeral head.

Additional treatment may be performed if deemed necessary by the researcher

[Objectives]

• Primary objective

• 5yr Disease Free Survival
• Secondary objectives

• 5yr Overall Survival
• 5yr Distant Metastasis Free Survival
• Axillary recurrence rate
• Patient reported AE
• QoL

Inclusion criteria

• Women ≥ 19 years
• Invasive unilateral breast carcinoma with histological confirmation
• History of invasive breast cancer
• Histologically or radiologically no suspicion of distant metastases
• Performance status corresponding to ECOG grade 0-2
• Tumor size clinically and radiologically ≤ 5cm, independent of hormone receptor and HER2 status
• Clinically and sonographically negative axillary lymph nodes before biopsy; core needle biopsy or fine needle aspiration of suspicious lymph node required
• BCS candidate with postoperative whole-breast irradiation and adequate systemic therapy
• No psychological and geographical restriction in follow-up
• Written informed consent

Exclusion criteria

• History of any cancer in the previous 5 years
• Bilateral breast cancer
• Invasive breast cancer treated with neoadjuvant therapy
• Tumor size clinically and radiologically > 5cm
• Mastectomy candidate
• Pregnancy and breastfeeding
• Male breast cancer
• Unable to understand and fill out questionnaires