Axillary Management in Breast Cancer Patients With Needle Biopsy Proven Nodal Metastases After Neoadjuvant Chemotherapy (ATNEC)

ATNEC - Axillary Management in T1-3N1M0 Breast Cancer Patients With Needle Biopsy Proven Nodal Metastases at Presentation After Neoadjuvant Chemotherapy

The aim of this study is 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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Sentinel Lymph Node; Neoplasm, Breast
• Intervention / Treatment: Radiation: Breast or chest wall radiotherapy; Procedure: Axillary lymph node dissection; Radiation: Axillary radiotherapy

Detailed Description

Background: The presence of cancer in the axillary lymph nodes on needle biopsy in patients with early stage breast cancer before neoadjuvant chemotherapy (NACT) has been the determinant of the need for axillary treatment (in the form of axillary lymph node dissection (ALND) or axillary radiotherapy (ART)) after completion of NACT. Treatment to the axilla damages lymphatic drainage from the arm and patients can subsequently develop lymphoedema, restricted shoulder movement, pain, numbness, and other sensory problems. As more effective chemotherapy is now available that results in complete eradication of cancer in the axilla in around 40 to 70% of patients, extensive axillary treatment might no longer be necessary in patients with no evidence of residual nodal disease.

Aim: 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.

Methods:

Study design: A pragmatic, phase 3, open, randomised, multicentre trial and embedded economic evaluation in which participants will be randomised in a 1:1 ratio.

Study population: T1-3N1M0 breast cancer patients aged 18 years or older, with needle biopsy proven nodal metastases, who after NACT have no residual cancer in the lymph nodes on dual tracer sentinel node biopsy and removal of at least 3 lymph nodes (sentinel nodes and marked involved node).

Intervention: All participants will receive human epidermal growth factor receptor 2 (HER2)-targeted treatment, endocrine therapy and radiotherapy to breast or chest wall, if indicated according to local guidelines. Patients in the intervention group will not receive further axillary treatment (ALND or ART), whereas those receiving standard care will receive axillary treatment (ALND or ART) as per local guidelines. Follow-up is annually for at least 5 years.

Outcomes: The co-primary outcomes are disease free survival(DFS) and self-reported lymphoedema defined as 'yes' to the two questions participants will be asked - 'arm heaviness during the past year' and 'arm swelling now' from the Lymphoedema and Breast Cancer Questionnaire at 5 years.

Secondary outcomes: arm function assessed by the QuickDASH (disabilities of the arm, shoulder and hand) questionnaire; health related quality of life assessed using euroqol EQ-5D-5L; axillary recurrence free interval (ARFI); local recurrence; regional (nodal) recurrence; distant metastasis; overall survival; contralateral breast cancer; non-breast malignancy; costs; quality adjusted life years (QALYs) and cost-effectiveness.

Sample size: A sample size of 1900 patients would have the ability to demonstrate a 3.5% non-inferiority margin with a 5% 1-sided significance level and 85% power, allowing for 7% non-collection of primary outcome data assuming a 90% 5-year disease free survival rate in the control arm. It would also be able to detect at least a 5% difference in proportion of patients with lymphoedema with 90% power, a 5% 2-sided significance level and allowing for 25% non-collection of primary outcome data over 5 years.

Analysis plan: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Time to event outcomes, including disease free survival and axillary recurrence free interval, will be assessed using Kaplan-Meier curves and compared using Cox proportional hazards models. The proportion of patients experiencing lymphoedema at 5 years will be compared across trial arms using a chi-squared test and a logistic regression model used to adjust for stratification variables. Arm morbidity and health related quality of life will be scored using the appropriate manuals and assessed using a longitudinal mixed model regression analysis if model assumptions valid or a standardised area-under-the-curve analysis. For economic evaluation, incremental cost per QALY gained at 5 years will be estimated.

Timelines for delivery: Total project duration is 120 months based on 6 months for set up; 60 months recruitment period (including an 18 months internal pilot phase); and 54 months for follow up, analysis, writing up and dissemination.

• Study Type: Interventional
• Enrollment (Estimated): 1900
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amit Goyal, MS, MD, FRCS; Phone Number: +44 1332785538; Email: amit.goyal@nhs.net

Study Locations

• Ireland
  • Dublin, Ireland, D04 T6F4
    • Recruiting
    • St Vincent's University Hospital - St Vincent's Healthcare Group
    • Contact: Michael Boland
  • Dublin, Ireland, D06 HH36
    • Recruiting
    • St Luke's Hospital - St Luke's Radiation Oncology Network
    • Contact: John Armstrong
  • Dublin, Ireland, D09 V2N0
    • Recruiting
    • Beaumont Hospital - Royal College of Surgeons in Ireland
  • Galway, Ireland, H91 YR71
    • Recruiting
    • Galway University Hospitals - Saolta University Health Care Group
    • Contact: Aoife Lowery
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Recruiting
    • Aberdeen Royal Infirmary - NHS Grampian
    • Contact: Beatrix Elsberger
  • Ashford, United Kingdom, TW15 3AA
    • Recruiting
    • Ashford Hospital - Ashford and St Peter's Hospitals NHS Foundation Trust
    • Contact: Anneliese Lawn
  • Ashton-under-Lyne, United Kingdom, OL6 9RW
    • Recruiting
    • Tameside General Hospital- Tameside and Glossop Integrated Care NHS Foundation Trust
    • Contact: Pardeep Arora
  • Ayr, United Kingdom, KA6 6DX
    • Recruiting
    • University Hospital Crosshouse - NHS Ayrshire and Arran
    • Contact: Graeme Lumsden
  • Basildon, United Kingdom, SS16 5NL
    • Recruiting
    • Basildon University Hospital - Mid and South Essex NHS Foundation Trust
    • Contact: Zina Aladili
  • Belfast, United Kingdom, BT9 7AB
    • Recruiting
    • Belfast City Hospital - Belfast Health and Social Care Trust
    • Contact: Gareth Irwin
  • Birmingham, United Kingdom, B15 2GW
    • Recruiting
    • QEHB- University Hospitals Birmingham NHS Foundation Trust
    • Contact: Daniel Henderson
  • Birmingham, United Kingdom, B18 7QH
    • Recruiting
    • City Hospital -Sandwell and West Birmingham NHS Trust
    • Contact: Fiona Hoar
  • Blackpool, United Kingdom
    • Recruiting
    • Blackpool Victoria Hospital - Blackpool Teaching Hospitals NHS Foundation Trust
    • Contact: Pasupathy Kiriparan
  • Bolton, United Kingdom, BL4 0JR
    • Recruiting
    • Royal Bolton Hospital - Bolton NHS Foundation Trust
    • Contact: Ricardo Pardo-Garcia
  • Bradford, United Kingdom, BD5 0NA
    • Recruiting
    • St Luke's Hospital - Bradford Teaching Hospitals NHS Foundation Trust
    • Contact: Richard Linforth
  • Brighton, United Kingdom, BN2 5BE
    • Recruiting
    • Royal Sussex County Hospital - University Hospitals Sussex NHS Foundation Trust
    • Contact: Rathinasabapathy Rathinaezhil
  • Bristol, United Kingdom, BS10 5NB
    • Recruiting
    • Southmead Hospital - North Bristol NHS Trust
    • Contact: Sasirekha Govindarajulu
  • Burnley, United Kingdom, BB10 2PQ
    • Recruiting
    • Burnley General Hospital- East Lancashire Hospitals NHS Trust
    • Contact: Inder Kumar
  • Cambridge, United Kingdom, CB2 0QQ
    • Recruiting
    • Addenbrooke'S Hospital - Cambridge University Hospitals Nhs Foundation Trust
    • Contact: John Benson
  • Cheltenham, United Kingdom, GL53 7AN
    • Recruiting
    • Cheltenham General Hospital - Gloucestershire General Hospitals NHS Foundation Trust
    • Contact: Charlotte Kallaway
  • Chester, United Kingdom, CH2 1HJ
    • Recruiting
    • Countess of Chester Hospital - Countess of Chester Hospital NHS Trust
    • Contact: Anita Hargreaves
  • Crewe, United Kingdom, CW1 4QJ
    • Recruiting
    • Leighton Hospital - Mid Cheshire NHS Foundation Trust
    • Contact: Susan Hignett
  • Darlington, United Kingdom, DL3 6HX
    • Recruiting
    • Darlington Memorial Hospital - County Durham and Darlington NHS Foundation Trust
    • Contact: Sanjana Masinghe
  • Derby, United Kingdom, DE22 3NE
    • Recruiting
    • Royal Derby Hospital- University Hospitals of Derby and Burton NHS Foundation Trust
    • Contact: Emanuele Garreffa
  • Doncaster, United Kingdom, DN2 5LT
    • Recruiting
    • Doncaster Royal Infirmary - Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust
    • Contact: Lynda Wyld
  • Dudley, United Kingdom, DY1 2HQ
    • Recruiting
    • Russell's Hall Hospital - The Dudley Group NHS Foundation Trust
    • Contact: Velin Voynov
  • Dumfries, United Kingdom, DG2 8RX
    • Recruiting
    • Dumfries and Galloway Royal Infirmary - NHS Dumfries and Galloway
    • Contact: Aisling Hennessy
  • Dunfermline, United Kingdom, KY12 0SU
    • Active, not recruiting
    • Queen Margert Hospital - NHS Fife
  • East Kilbride, United Kingdom, G75 8RG
    • Recruiting
    • University Hospital Hairmyres - NHS Lanarkshire
    • Contact: Tareq Abdullah
  • Edinburgh, United Kingdom, EH4 2XU
    • Recruiting
    • Western General Hospital -NHS Lothian
    • Contact: Carolyn Bedi
  • Exeter, United Kingdom, EX2 5DW
    • Recruiting
    • Royal Devon & Exeter Hospital - Royal Devon and Exeter NHS Foundation Trust
    • Contact: Douglas Ferguson
  • Gateshead, United Kingdom, NE9 6SX
    • Recruiting
    • Queen Elizabeth Hospital - Gateshead Health NHS Foundation Trust
    • Contact: Sunil Amonkar
  • Glasgow, United Kingdom, G12 0YN
    • Recruiting
    • Beatson West of Scotland Cancer Centre - Greater Glasgow Health Board
    • Contact: Rosemary Stevens
  • Guildford, United Kingdom, GU2 7XX
    • Recruiting
    • Royal Surrey County Hospital - Royal Surrey NHS Foundation Trust
    • Contact: Jonathan Horsnell
  • Harrogate, United Kingdom, HG2 7SX
    • Recruiting
    • Harrogate District Hospital - Harrogate and District NHS Foundation Trust
    • Contact: Biswajit Ray
  • Hereford, United Kingdom, HR1 2ER
    • Recruiting
    • Hereford County Hospital- Wye Valley NHS Trust
    • Contact: Kaustuv Das
  • High Wycombe, United Kingdom, HP11 2TT
    • Recruiting
    • Wycombe Hospital - Buckinghamshire Healthcare NHS Trust
    • Contact: Nicholas Holford
  • Huddersfield, United Kingdom, HD3 3EA
    • Recruiting
    • Huddersfield Royal Infirmary- Calderdale and Huddersfield NHS Foundation Trust
    • Contact: Werbena Hamilton-Burke
  • Hull, United Kingdom, HU16 5JQ
    • Recruiting
    • Castle Hill Hospital - Hull University Teaching Hospitals NHS Trust
    • Contact: Kartikae Grover
  • Ipswich, United Kingdom, IP4 5PD
    • Recruiting
    • Ipswich Hospital - East Suffolk and North Essex NHS Foundation Trust
    • Contact: Hussein Tuffaha
  • Isleworth, United Kingdom, TW7 6AF
    • Recruiting
    • West Middlesex University Hospital - Chelsea and Westminster Hospital NHS Foundation Trust
    • Contact: Musa Barkeji
  • Lancaster, United Kingdom, LA1 4RP
    • Recruiting
    • Royal Lancaster Infirmary - University Hospitals of Morecambe Bay NHS Foundation Trust
    • Contact: Rishi Parmeshwar
  • Larbert, United Kingdom, FK5 4WR
    • Recruiting
    • Forth Valley Royal Hospital - NHS Forth Valley
    • Contact: Subodh Seth
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • St James's University Hospital - Leeds Teaching Hospitals NHS Trust
    • Contact: Emma MacInnes
  • Leicester, United Kingdom, LE3 9QP
    • Recruiting
    • Glenfield Hospital - University Hospitals of Leicester NHS Trust
    • Contact: Monika Kaushik
  • Lincoln, United Kingdom, LN2 5QY
    • Active, not recruiting
    • Lincoln County Hospital - United Lincolnshire Hospitals NHS Trust
  • Llanelli, United Kingdom, SA14 8QF
    • Recruiting
    • Prince Phillip Hospital -Hywel Dda University Health Board
    • Contact: Saira Khawaja
  • London, United Kingdom, SM2 5PT
    • Recruiting
    • The Royal Marsden NHS Foundation Trust
    • Contact: Katherine Krupa
  • London, United Kingdom, N18 1QX
    • Recruiting
    • North Middlesex University Hospital - North Middlesex University Hospital NHS Trust
    • Contact: Lai Cheng Yew
  • London, United Kingdom, N19 5NF
    • Recruiting
    • The Whittington Hospital - Whittington Health NHS Trust
    • Contact: Irene Athanasiou
  • London, United Kingdom, NW1 2BU
    • Active, not recruiting
    • UCL Hospital - University College London Hospitals NHS Foundation Trust
  • London, United Kingdom, NW3 2QG
    • Recruiting
    • Royal Free Hospital - Royal Free London NHS Foundation Trust
    • Contact: Debashis Ghosh
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Kings College Hospital - King's College Hospital NHS Foundation Trust
    • Contact: Neeraj Garg
  • London, United Kingdom, W6 8RF
    • Recruiting
    • Charing Cross Hospital -Imperial College Healthcare NHS Trust
    • Contact: Daniel Leff
  • Luton, United Kingdom, LU4 0DZ
    • Recruiting
    • Luton and Dunstable Hospital -Bedfordshire Hospitals NHS Foundation Trust
    • Contact: Ruth James
  • Manchester, United Kingdom, M23 9LT
    • Recruiting
    • Wythenshawe Hospital - Manchester University Hospital NHS Foundation Trust
    • Contact: Anjana Satpathy
  • Manchester, United Kingdom, M8 5RB
    • Recruiting
    • North Manchester General -Manchester University NHS Foundation Trust
    • Contact: Anjana Satpathy
  • Melrose, United Kingdom, TD6 9BS
    • Recruiting
    • Borders General Hospital -NHS Borders
    • Contact: Carolyn Bedi
  • Metropolitan Borough of Wirral, United Kingdom, CH63 4JY
    • Recruiting
    • Clatterbridge Cancer Centre - The Clatterbridge Cancer Centre NHS Foundation Trust
    • Contact: Shaveta Mehta
  • Metropolitan Borough of Wirral, United Kingdom, CH63 4JY
    • Recruiting
    • Clatterbridge Hospital - Wirral University Teaching Hospital NHS Foundation Trust
    • Contact: Raman Vinayagam
  • Middlesbrough, United Kingdom, TS4 3BW
    • Recruiting
    • The James Cook University Hospital - South Tees Hospitals NHS Foundation Trust
    • Contact: Brinda Sethugavalar
  • Milton Keynes, United Kingdom, MK6 5LD
    • Recruiting
    • Milton Keynes Hospital - Milton Keynes University Hospital NHS Trust
    • Contact: Amanda Taylor
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Recruiting
    • Royal Victoria Infirmary- Newcastle Upon Tyne Hospitals NHS Foundation Trust
    • Contact: Henry Cain
  • North Shields, United Kingdom, NE29 8NH
    • Recruiting
    • North Tyneside General Hospital - Northumbria Healthcare NHS Foundation Trust
    • Contact: Grant Harris
  • Oxford, United Kingdom, OX3 7LE
    • Recruiting
    • Churchill Hospital - Oxford University Hospitals NHS Foundation Trust
    • Contact: Pankaj Roy
  • Paisley, United Kingdom, PA2 9PN
    • Recruiting
    • Royal Alexandra Hospital - NHS Greater Glasgow and Clyde
    • Contact: Abdulla Alhasso
  • Plymouth, United Kingdom, PL6 8DH
    • Recruiting
    • Derriford Hospital - University Hospitals Plymouth NHS Trust
    • Contact: Saed Ramzi
  • Portsmouth, United Kingdom, PO6 3LY
    • Recruiting
    • Queen Alexandra Hospital - Portsmouth Hospitals University NHS Trust
    • Contact: Edward St John
  • Prescot, United Kingdom, L35 5DR
    • Recruiting
    • St Helen's Hospital - St Helens and Knowsley Teaching Hospitals NHS Trust
    • Contact: Tamara Kiernan
  • Preston, United Kingdom, PR2 9HT
    • Recruiting
    • Royal Preston Hospital - Lancashire Teaching Hospitals NHS Foundation Trust
    • Contact: Bade Murthy
  • Redhill, United Kingdom, RH1 5RH
    • Recruiting
    • East Surrey Hospital - Surrey & Sussex Healthcare NHS Trust
    • Contact: Jagdeep Singh
  • Rotherham, United Kingdom, S60 2UD
    • Recruiting
    • Rotherham General Hospital - The Rotherham NHS Foundation Trust
    • Contact: Tahir Masudi
  • Sheffield, United Kingdom, S10 2SJ
    • Recruiting
    • Weston Park Hospital - Sheffield Teaching Hospitals NHS Foundation Trust
    • Contact: George Boundouki
  • St Albans, United Kingdom, AL3 5PN
    • Recruiting
    • St Alban's Hospital - West Hertfordshire Hospitals NHS Trust
    • Contact: Lee Min Lai
  • Stevenage, United Kingdom, SG1 4AB
    • Recruiting
    • Lister Hospital - East and North Hertfordshire NHS Foundation Trust
    • Contact: Muhammed Baki
  • Stockton-on-Tees, United Kingdom, TS19 8PE
    • Recruiting
    • University Hospital North Tees - North Tees and Hartlepool NHS Foundation Trust
    • Contact: Matei Dordea
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Recruiting
    • Royal Stoke University Hospital - University Hospitals of North Midlands NHS Trust
    • Contact: Sekhar Marla
  • Swansea, United Kingdom, SA2 8QA
    • Recruiting
    • Singleton hospital - Swansea Bay University Health Board
    • Contact: Konstantinos Serafeimidis
  • Taunton, United Kingdom, TA1 5DA
    • Recruiting
    • Musgrove park Hospital -Somerset NHS Foundation Trust
    • Contact: Zoe Goldthorpe
  • Thornton Heath, United Kingdom, CR7 7YE
    • Recruiting
    • Croydon University Hospital - Croydon Health Services NHS Trust
    • Contact: Lubna Noor
  • Truro, United Kingdom, TR1 3LJ
    • Recruiting
    • Royal Cornwall Hospital - Royal Cornwall Hospitals NHS Trust
    • Contact: Alastair Thomson
  • Uxbridge, United Kingdom, UB8 3NN
    • Recruiting
    • Hillingdon Hospital - The Hillingdon Hospitals NHS Foundation Trust
    • Contact: Arunmoy Chakravorty
  • Wakefield, United Kingdom, WF1 4DG
    • Recruiting
    • Pinderfields Hospital - Mid Yorkshire Hospitals NHS Trust
    • Contact: Daniel Glassman
  • Westcliff-on-Sea, United Kingdom, SS0 0RY
    • Recruiting
    • Southend Hospital and Broomfield Hospital -Mid and South Essex NHS Foundation Trust
    • Contact: Abdul Syed
  • Wigan, United Kingdom, WN1 2NN
    • Recruiting
    • Royal Albert Edward Infirmary - Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust
    • Contact: Konstantinos Zacharioudakis
  • Windsor, United Kingdom, SL4 3DP
    • Recruiting
    • King Edward VII Hospital - Frimley Health NHS Foundation Trust
    • Contact: kaiyumars Contractor
  • Wolverhampton, United Kingdom, WV10 0QP
    • Recruiting
    • New Cross Hospital - The Royal Wolverhampton NHS Trust
    • Contact: Raghavan Vidya
  • Worcester, United Kingdom, WR5 1JR
    • Recruiting
    • Worcestershire Royal Hospital - Worcestershire Acute Hospitals NHS Trust
    • Contact: Steven Thrush
  • Yeovil, United Kingdom, BA21 4AT
    • Recruiting
    • Yeovil District Hospital -Yeovil District Hospital NHS Trust
    • Contact: Caroline Osborne
  • York, United Kingdom, YO31 8HE
    • Recruiting
    • York Hospital - York and Scarborough Teaching Hospitals NHS Foundation Trust
    • Contact: Bhavani Rengabashyam
  • BD20 6TD
    • Keighley, BD20 6TD, United Kingdom
      • Recruiting
      • Airedale General Hospital - Airedale NHS Foundation Trust
      • Contact: Claire Murphy
  • CA2 7HY
    • Carlisle, CA2 7HY, United Kingdom
      • Recruiting
      • Cumberland Infirmary - North Cumbria Integrated Care NHS Foundation Trust
      • Contact: Ludger Barthelmes
  • GU16 7UJ
    • Camberley, GU16 7UJ, United Kingdom
      • Recruiting
      • Frimley Park Hospital - Frimley Health NHS Foundation Trust
      • Contact: kaiyumars Contractor
      • Contact: Hisham Osman
  • IV2 3UJ
    • Inverness, IV2 3UJ, United Kingdom
      • Recruiting
      • Raigmore Hospital - NHS Highland
      • Contact: Eileen Anderson
  • NR31 6LA
    • Great Yarmouth, NR31 6LA, United Kingdom
      • Recruiting
      • James Paget Hospital -James Paget University Hospitals NHS Foundation Trust
      • Contact: Sue Down
  • RG1 5AN
    • Reading, RG1 5AN, United Kingdom
      • Recruiting
      • Royal Berkshire Hospital - Royal Berkshire NHS Foundation Trust
      • Contact: Brendan Smith
  • SK10 3BL.
    • Macclesfield, SK10 3BL., United Kingdom
      • Recruiting
      • Macclesfield District General Hospital - East Cheshire NHS Trust
      • Contact: Jalal Kokan
  • SY3 8XQ
    • Shrewsbury, SY3 8XQ, United Kingdom
      • Recruiting
      • Royal Shrewsbury Hospital -The Shrewsbury and Telford Hospitals NHS Trust
      • Contact: Laura Pettit

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18
• Male or female

• cT1-3N1M0 breast cancer at diagnosis (prior to NACT) as per AJCC 8th edition (see Section 6.4.1)

  o Patients with occult primary invasive breast cancer (no identifiable invasive cancer in the breast) with FNA or core biopsy proven nodal metastases are eligible for the study.

• 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)
• Imaging of the axilla, as required, to assess response to NACT (per local guidelines)

• Undergo a dual tracer sentinel node biopsy (SNB) after NACT with at least 3 nodes removed.

  • If a single tracer SNB is performed: the patient is eligible only if the involved node is marked before or during NACT, and at least 3 nodes (including the marked node) are removed during sentinel node biopsy.
  • If the node is not marked or the marked node is not removed: the patient is eligible only 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.

  • If fewer than 3 nodes are found on histology: the patient is eligible only if BOTH points a) and b), below, are met:

    1. involved node was marked and removed during SNB; and
    2. removed marked node shows evidence of downstaging on histology e.g. fibrosis or scarring.
• If the sentinel node(s) cannot be localised on SNB: axillary node sampling should be performed, the patient will be eligible if at least 3 nodes are removed.
• No evidence of nodal metastases post NACT (isolated tumour cells, micro or macro metastasis)
• Patients with complete pathological response in the axilla but residual disease in the breast post NACT are eligible for the study
• Patients who are cN0 (node negative) at initial presentation, with a negative sentinel node post NACT showing evidence of treatment response or downstaging will be eligible, provided at least 3 nodes are removed.

5.2. Exclusion Criteria

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

• Bilateral synchronous invasive breast cancer
• Sentinel node biopsy prior to NACT
• Previous axillary nodal 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
  • chronic lymphocytic leukaemia not on treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: No axillary treatment; Patients in this arm will not receive axillary treatment (axillary lymph node dissection or axillary radiotherapy). Supraclavicular fossa radiotherapy is not allowed when randomised to this arm.	Radiation: Breast or chest wall radiotherapy; Breast or chest wall radiotherapy will be delivered as per the Radiotherapy Trials Quality Assurance (RTTQA) guidelines.
Active Comparator: Axillary treatment; Patients in this arm will receive axillary treatment. Axillary treatment can be axillary lymph node dissection or axillary radiotherapy.	Radiation: Breast or chest wall radiotherapy; Breast or chest wall radiotherapy will be delivered as per the Radiotherapy Trials Quality Assurance (RTTQA) guidelines.; Procedure: Axillary lymph node dissection; Participants will undergo removal of at least level I and II axillary lymph nodes.; Radiation: Axillary radiotherapy; Axillary radiotherapy will be delivered as per the Radiotherapy Trials Quality Assurance (RTTQA) guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival (DFS)	DFS calculated as the time from randomisation until the date of first event of either a loco-regional invasive breast cancer relapse, distant relapse, ipsilateral or contralateral new invasive primary breast cancer or death by any cause or the censor date.	5 years
Patient reported lymphoedema	Lymphoedema is self-reported based on two items from the validated Lymphoedema and Breast Cancer Questionnaire (arm "swelling now" and arm "heaviness in the past year"). Lymphoedema is defined as 'yes' to both questions.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arm function	Arm function will be assessed using shortened version of the Disability of the Arm, Shoulder and Hand (DASH), the 11-item QuickDASH questionnaire. Physical disability is defined as a change from baseline in the QuickDASH score of at least 14 points.	5 years
Health related quality of life: EQ-5D-5L	Health related quality of life will be assessed with EQ-5D-5L	5 years
Axillary recurrence free interval	Axillary recurrence free interval, calculated from the date of randomisation to the date of axillary recurrence or the censor date.	5 years
Overall survival	Overall survival calculated as the time from randomisation until the date of death by any cause or the censor date.	5 years
Local (breast or chest wall) recurrence	Number of participants with local (breast or chest wall) recurrence	5 years
Regional (nodal) recurrence	Number of participants with regional (nodal) recurrence	5 years
Distant metastasis	Number of participants with distant metastasis.	5 years
Contralateral breast cancer	Number of participants with contralateral breast cancer.	5 years
Non-breast cancer	Number of participants with non-breast cancer	5 years

Collaborators and Investigators

• Sponsor: University Hospitals of Derby and Burton NHS Foundation Trust
• Investigators: Principal Investigator: Amit Goyal, MS, MD, FRCS, Royal Derby Hospital, Derby, UK

Publications and helpful links

Helpful Links

• Training video for surgeons to remove the marked node during sentinel node biopsy
• Training video for radiologists to mark the node using black dye tattoo
• Training video for radiologists to mark the node using clip
• ATNEC breast cancer study - Research Nurse and Patient Consultation
• ATNEC breast cancer study - Example Doctor and Patient Consultation

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2021
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): February 28, 2030

Study Registration Dates

• First Submitted: September 27, 2019
• First Submitted That Met QC Criteria: September 27, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; neoadjuvant chemotherapy; sentinel node biopsy; tattooing node; marking node; clip node; axillary ultrasound; node positive; axillary lymph node dissection; axillary radiotherapy; axillary treatment
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: NIHR 128311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No