ATNEC

ATNEC

Axillary management in T1-3N1M0 breast cancer patients with needle biopsy proven nodal metastases at presentation after neoadjuvant chemotherapy.

Overview

ATNEC is a phase III, open, randomised, multicentre trial comparing standard axillary treatment (either, axillary lymph node dissection [ALND] or axillary radiotherapy [ART]) with no axillary treatment post-surgery, in early stage (T1-3N1M0) breast cancer patients.

Currently, the presence of axillary lymph node metastases on needle biopsy, prior to neoadjuvant chemotherapy (NACT), is the determinant for whether a patient requires further axillary treatment (ALND or ART) post-surgery.

Axillary treatment damages lymphatic drainage from the arm and can cause life-long side effects such as lymphoedema, restricted shoulder movement or discomfort, pain, sensory changes and numbness. These adverse events interfere with daily activities, impair quality of life and are costly to the NHS in terms of rehabilitative treatments.

As more effective NACT is now available, that results in complete eradication of cancer in the axilla in 40% to 70% of patients, extensive axillary treatment may no longer be necessary in patients with no evidence of residual nodal disease. The ATNEC study aims to address this question.

Objectives

Primary objective:

-To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy, who after NACT have no residual cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years.  

Secondary objectives:

• To compare arm morbidity and quality of life between and within the two allocated groups over five years.
• To compare axillary recurrence free interval, breast or chest wall recurrence, regional (nodal) recurrence, distant metastasis, and overall survival, contralateral breast cancer, non-breast malignancy between the two allocated groups over five years.

Economic Evaluation

• To compare costs to the NHS and to participants over five years
• To compare quality-adjusted life years (QALYs) over five years
• To estimate cost-effectiveness measured in terms of incremental cost per disease free interval from the perspective of the NHS and patients over five years
• To estimate cost-effectiveness measured in terms of incremental cost per lymphoedema event avoided from the perspective of the NHS and patients over five years
• To estimate cost-effectiveness measured in terms of incremental cost per QALY gained from the perspective of the NHS and patients over five years
• To extrapolate costs and outcomes over the lifetime of patients with early stage breast cancer and estimate the cost-effectiveness measured in terms of incremental cost per QALY gained from the perspective of the NHS and patients
  Qualitative Evaluation
• To identify and investigate recruitment issues and develop effective and realistic strategies to ensure overall success of the trial 

Inclusion Criteria:

Eligible participants will be/should have:

• Age ≥ 18
• Male or female
• T1-3N1M0 breast cancer at diagnosis (prior to NACT)
• FNA or core biopsy confirmed axillary nodal metastases at presentation
• Oestrogen receptor and HER2 status evaluated on primary tumour
• Received standard NACT as per local guidelines (Patients undergoing neoadjuvant endocrine therapy as part of another clinical trial are eligible)
• Ultrasound of the axilla to assess response to NACT (Not required if axilla assessed by other imaging technique).
• Undergo dual tracer sentinel node biopsy after NACT and at least 3 nodes removed (sentinel nodes and marked node).
• If a single tracer is used, the patient will be eligible if the involved node is marked before NACT, and the marked node and at least 3 nodes (including the marked node) are removed during sentinel node biopsy.
• If axillary node sampling is performed following failed localisation of sentinel nodes, patient will be eligible if at least 3 nodes are removed (including the marked node).
• If node is not marked, or marked node is not removed, the patient will be eligible if the histology report shows evidence of down-staging with complete pathological response e.g. fibrosis or scarring in at least one node and at least 3 nodes removed.
• No evidence of nodal metastases post NACT (isolated tumour cells, micro or macro metastasis)

Exclusion Criteria:

Participants will be excluded if they have any one of the following:

• Bilateral invasive breast cancer
• Sentinel node biopsy prior to NACT
• Previous axillary surgery on the same body side as the scheduled targeted sampling
• Any previous cancer within last 5 years or concomitant malignancy except

• basal or squamous cell carcinoma of the skin
• in situ carcinoma of the cervix
• in situ or stage 1 melanoma
• contra- or ipsilateral in situ breast cancer

Planned sample size:

1900 participants (950 per arm) will be randomised (1:1) to either standard axillary treatment (ALND or ART), or no further axillary treatment.  

Approximately 100 sites planned.

ATNEC is open to the addition of new sites and still accepting expressions of interest, contact the study team for more information (ATNEC@warwick.ac.uk).

Timeline

ATNEC has a planned recruitment period of 5 years from December 2020 to December 2025 and a minimum 5-year follow up period (study end date February 2030).