ATNEC - Axillary management in T1-3N1M0 breast cancer patients with needle biopsy-proven nodal metastases at presentation after neoadjuvant chemotherapy
| ISRCTN | ISRCTN36585784 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN36585784 |
| IRAS number | 280105 |
| ClinicalTrials.gov number | NCT04109079 |
| Secondary identifying numbers | CPMS 46520, IRAS 280105 |
- Submission date
- 26/10/2020
- Registration date
- 02/12/2020
- Last edited
- 05/02/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English Summary
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-further-treatment-to-the-armpit-after-surgery-to-remove-breast-cancer-atnec
Background and study aims
Early-stage breast cancer patients with abnormal-looking armpit lymph glands on an ultrasound scan will have a sample (needle biopsy) of this lymph gland taken. If the sample shows cancer cells are present, patients are often given chemotherapy before surgery (called neoadjuvant chemotherapy) to shrink these cancer cells before their operation. Currently after chemotherapy, all patients undergo breast surgery (lumpectomy or mastectomy) and treatment to their armpit (either removal of all armpit lymph glands or radiotherapy to the armpit).
Neoadjuvant chemotherapy results in complete disappearance of cancer in the lymph glands in around 40-70% of patients. For these patients there may be no extra benefit from more treatment to their armpit. Any extra armpit treatment may damage lymphatic drainage from the arm, which could lead to arm swelling (lymphoedema), restricted shoulder movement, pain, numbness and other sensory problems. These side effects make some daily activities difficult for patients, they are distressing and affect their quality of life. They are costly to the NHS in terms of treatments such as physiotherapy and attendance at lymphoedema clinics.
The aim of this study is to find out whether stopping further armpit treatment for patients with no cancer in the lymph glands after chemotherapy is safe, in terms of risk of cancer coming back and fewer lymphoedema cases at 5 years. After neoadjuvant chemotherapy and at the time of breast surgery, patients will undergo removal of at least three lymph glands from the armpit. If there is no cancer in the removed glands, patients will be randomly allocated to receive standard armpit treatment or no further treatment to the armpit.
Results of this study could benefit patients by avoiding unnecessary treatment to the armpit and thus reducing future problems with the arm and shoulder, and possibly improved quality of life and reduced healthcare costs.
Who can participate?
Patients aged 18 or older with early-stage breast cancer that has spread to the lymph gland in their armpit, who will receive (or has received) standard neoadjuvant chemotherapy
What does the study involve?
Eligibility for the randomised portion of the trial will be assessed following completion of neoadjuvant chemotherapy and surgery. The patient’s clinician will assess how well their cancer has responded to treatment. If following these assessments, there is no remaining sign of cancer in the patient’s armpit lymph glands, then they will be deemed eligible to take part in the randomised stage of the study. Patients eligible for the study will receive either:
1. No further treatment to your armpit, following neoadjuvant chemotherapy and breast surgery, or
2. Further treatment to your armpit, following neoadjuvant chemotherapy and breast surgery
Which treatment patients receive (option 1 or option 2) is decided by a process called randomisation. Neither patients nor their doctor will be able to choose which group is assigned; treatment allocation will be decided randomly by a computer.
If a patient is allocated further treatment to their armpit (option 2), they, together with their doctor, can choose either surgery to remove all remaining lymph glands in the armpit or radiotherapy to the armpit area.
All participants, regardless of which group they are allocated to, will still receive other standard treatment for their breast cancer, such as radiotherapy to the breast and chest wall, and hormone therapy. This treatment will be given as indicated, upon the advice of the clinical team.
Patients who are eligible for the study will also be asked to complete a short questionnaire booklet; there will be five further questionnaire booklets to complete over the course of the study. The researchers will use the responses to assess how patients are feeling with respect to their treatment. Each questionnaire should take approximately 20 minutes to complete.
What are the possible benefits and risks of participating?
The researchers cannot promise that this study will help participants, but it may help patients in the future. Findings from this study will also help inform the future care of patients with early breast cancer that has spread to the armpit. The researchers do not know whether removing further armpit treatment, if there are no signs of cancer left in patients’ lymph glands, will have an impact on the risk of their cancer returning – that is why they are doing the study. All participants will be closely monitored by their clinical care team, and if there is any sign of cancer recurrence, their doctor will discuss the best course of action.
X-rays, nuclear medicine imaging and radiotherapy, where appropriate, are part of patients’ routine care. If patients take part in this study, they will not undergo any additional imaging or radiotherapy. These procedures use ionising radiation to form images of the body and/or provide treatment and/or provide doctors with other clinical information. Ionising radiation can cause cell damage that may, after many years or decades, turn cancerous. Patients’ doctors will discuss other possible side-effects of radiotherapy with them. The chances of these things happening to patients are the same whether they take part in this study or not.
Participants will be asked to complete questionnaires which will take some of their time (about 20 minutes per questionnaire). As the questionnaires form a key part of our data collection for the study, it is important for participants to consider whether they will have the time to complete these fully. Participants will be issued with one questionnaire booklet at trial entry and then five further questionnaires at the following time points: 1 year, 2 years, 3 years, 4 years and 5 years.
Where is the study run from?
University Hospitals of Derby and Burton NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
March 2020 to March 2030
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
ATNEC Trial Management team
ATNEC@warwick.ac.uk
Contact information
Scientific
Chief Investigator
Royal Derby Hospital
Derby
DE22 3NE
United Kingdom
 ORCID ID |
0000-0002-2381-8337 |
|---|---|
| Phone | +44 (0)1332 785538 |
| amit.goyal@nhs.net |
Public
ATNEC Trial Manager
Warwick Clinical Trials Unit
University of Warwick
Coventry
CV4 7AL
United Kingdom
| Phone | +44 (0)2476524438 |
|---|---|
| ATNEC@warwick.ac.uk |
Study information
| Study design | Randomized; Both; Design type: Treatment, Process of Care, Surgery, Other, Health Economic |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details or speak to the local hospital care team to request a participant information sheet |
| Scientific title | ATNEC - Axillary management in T1-3N1M0 breast cancer patients with needle biopsy-proven nodal metastases at presentation after neoadjuvant chemotherapy |
| Study acronym | ATNEC |
| Study hypothesis | 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, will be non-inferior to axillary treatment in terms of disease-free survival (DFS) and will result in a reduced risk of lymphoedema at 5 years. |
| Ethics approval(s) |
Approved 22/10/2020, Yorkshire & The Humber – Bradford Leeds Research Ethics Committee (Newcastle Blood Donor Centre, Holland Drive, HRA Newcastle, Newcastle, NE2 4NQ, United Kingdom; +44 (0)207 104 8083, +44 (0)207 104 8088, +44 (0)207 104 8018; bradfordleeds.rec@hra.nhs.uk), ref: 20/YH/0232 |
| Condition | Breast cancer |
| Intervention | Current interventions as of 19/07/2023: ATNEC is a multi-centre, randomised clinical trial with a non-inferiority endpoint and a pragmatic design. ATNEC will be conducted in patients with early-stage, node-positive breast cancer, whose usual treatment pathway would be neoadjuvant chemotherapy followed by breast surgery and further treatment to the armpit (lymph node clearance or radiotherapy to the armpit). Patients who have no residual cancer in the lymph glands after chemotherapy will be randomised to either have standard armpit treatment or no further treatment to the armpit. An integrated feasibility study, with embedded qualitative research, will assess the willingness of clinicians and patients to participate in the ATNEC trial. Pre-Randomisation: To be eligible, a patient must be diagnosed with early-stage, confirmed node-positive breast cancer on needle biopsy, and planned to receive chemotherapy first (neoadjuvant chemotherapy) prior to surgery. The patient’s primary tumour must have been evaluated for receptor status. Patients can be either female or male, and must be aged 18 years or older. Patients who are confirmed to be eligible will be invited to take part in the study and if, following review of the patient information sheet, they decide to participate, written informed consent will be obtained. Once a patient has consented to participate, the site team will be able to register them to the study via the ATNEC online registration portal. The patient will be assigned a unique trial number, which will be used to identify them throughout the study. It is recommended that the patient’s clinical team will mark the abnormal armpit lymph gland – this could be done either by using a clip, carbon dye or by inserting a magnetic seed as per local practice. Patients will then continue to receive neo-adjuvant chemotherapy, as per standard practice. Following the completion of their chemotherapy, patients will undergo imaging assessment of the lymph glands to check for abnormal-looking lymph glands. If the armpit lymph glands are found to still contain residual cancer cells, the patient will not be eligible for randomisation and will continue with treatment for their cancer, per standard practice. If the ultrasound shows no confirmed evidence of residual cancer, then the patient will proceed to breast surgery (either lumpectomy to remove the lump, or mastectomy to remove the breast). During their operation, a procedure called a sentinel lymph node biopsy will also be performed; this will involve the removal of at least three lymph glands (including the original marked gland). The removed glands will be tested to provide definitive confirmation that the patient has no remaining cancer in their armpit glands. At this point, the patient will be deemed eligible for randomisation. Patients who are deemed eligible, but have not previously been registered, can also enter the trial at this point. Patients who are willing to participate will be consented after their surgery, registration and randomisation will take place as one process. Randomisation/Baseline: Prior to randomisation, patients will be issued with a baseline questionnaire booklet containing the following questionnaires: the lymphoedema and breast cancer questionnaire (LBCQ), a shortened version of the Disability of the Arm, Shoulder and Hand (QuickDASH) questionnaire, a health utilisation questionnaire, and the EQ-5D-5L questionnaire which captures information about a patient’s overall health state. Eligible patients, with continuing consent, will be randomised to the study via the online ATNEC randomisation portal. Patients will be randomised to receive either standard treatment to the armpit (lymph node clearance or radiotherapy to the armpit) or no further armpit treatment. Follow-Up: Patients are required to complete five further questionnaire booklets: at 1 year, 2 years, 3 years, 4 years and 5 years post-randomisation. These questionnaire booklets will be posted directly to patients by Warwick Clinical Trials Unit, to complete at home. Posted questionnaires will include a pre-paid return envelope, so completed questionnaires can be returned to the Warwick Clinical Trials Unit. Beyond the first year, sites will be asked to follow-up patients annually for at least 5 years. Follow-up can be by capturing information from hospital records or by telephone if the treating site has discharged the patient from clinical follow-up. After 5 years, follow-up information will be sought from NHS Digital health records, so long as the patient has given their consent for this. Radiotherapy Quality Assurance Component: The ATNEC trial will have an embedded radiotherapy quality assurance programme, coordinated by the National Radiotherapy Quality Assurance (RTTQA) group. Sites will be required to adhere to the specific radiotherapy planning and delivery guidelines, developed by the RTTQA team. Qualitative Sub-Study: Qualitative research has been embedded within the recruitment phase to identify and investigate recruitment issues and develop effective and realistic strategies to ensure the success of the trial. Participation in any aspect of the qualitative sub-study is optional. Patients who appear eligible for ATNEC will be asked for their permission to audio-record their conversations with their doctor up until the point that they make their decision on whether or not to participate. Prior to any commencement of recording, patients will be given a brief patient information sheet explaining the qualitative sub-study. Patients will be given sufficient time to review this and ask any questions. If patients agree to be recorded, they will be asked to sign a consent form, providing permission for the audio-recordings of their consultations. In addition, patients who were invited to take part in ATNEC (including those who declined to take part) may be invited for interview at a later date to discuss the reasons why they may, or may not, have chosen to take part in the trial. A separate patient information sheet will be provided for this purpose and, should the patient be happy to be interviewed, written informed consent will be obtained. Patients will be asked for their permission to have their interview audio-recorded. This permission is covered in the above-mentioned patient information sheet and informed consent form. It will be made explicitly clear to patients, at the time of their consultation, or following the informed consent process for the trial, that their participation in the qualitative sub-study is completely optional. The decision of patients who decline to take part will be completely respected, and their medical care will not be affected in any way. Researchers who are involved in the ATNEC trial consent process (i.e clinicians and research nurses) will also be invited for an interview. Research staff will also be provided with an information sheet and their informed consent will be required prior to any audio-recording of patient consultations and/or interviews. An overall plan for the qualitative sub-study, including timelines for interviews, is attached to this application. _____ Previous interventions: ATNEC is a multi-centre, randomised clinical trial with a non-inferiority endpoint and a pragmatic design. ATNEC will be conducted in patients with early-stage, node-positive breast cancer, whose usual treatment pathway would be neoadjuvant chemotherapy followed by breast surgery and further treatment to the armpit (lymph node clearance or radiotherapy to the armpit). Patients who have no residual cancer in the lymph glands after chemotherapy will be randomised to either have standard armpit treatment or no further treatment to the armpit. An integrated feasibility study, with embedded qualitative research, will assess the willingness of clinicians and patients to participate in the ATNEC trial. Pre-Randomisation: To be eligible, a patient must be diagnosed with early-stage, confirmed node-positive breast cancer on needle biopsy, and planned to receive chemotherapy first (neoadjuvant chemotherapy) prior to surgery. The patient’s primary tumour must have been evaluated for receptor status. Patients can be either female or male, and must be aged 18 years or older. Patients who are confirmed to be eligible will be invited to take part in the study and if, following review of the patient information sheet, they decide to participate, written informed consent will be obtained. Once a patient has consented to participate, the site team will be able to register them to the study via the ATNEC online registration portal. The patient will be assigned a unique trial number, which will be used to identify them throughout the study. Prior to receiving treatment, the patient’s clinical team will mark the abnormal armpit lymph gland – this could be done either by using a clip, carbon dye or by inserting a magnetic seed as per local practice. Patients will then continue to receive neo-adjuvant chemotherapy, as per standard practice. Following the completion of their chemotherapy, patients will undergo an ultrasound scan of the lymph glands to check for abnormal-looking lymph glands and if needed needle biopsy. If the armpit lymph glands are found to still contain residual cancer cells, the patient will not be eligible for randomisation and will continue with treatment for their cancer, per standard practice. If the ultrasound shows no confirmed evidence of residual cancer, then the patient will proceed to breast surgery (either lumpectomy to remove the lump, or mastectomy to remove the breast). During their operation, a procedure called a sentinel lymph node biopsy will also be performed; this will involve the removal of at least three lymph glands (including the original marked gland). The removed glands will be tested to provide definitive confirmation that the patient has no remaining cancer in their armpit glands. At this point, the patient will be deemed eligible for randomisation. Patients who are deemed eligible, but have not previously been registered, can also enter the trial at this point. Patients who are willing to participate will be consented after their surgery, registration and randomisation will take place as one process. Randomisation/Baseline: Prior to randomisation, patients will be issued with a baseline questionnaire booklet containing the following questionnaires: the lymphoedema and breast cancer questionnaire (LBCQ), a shortened version of the Disability of the Arm, Shoulder and Hand (QuickDASH) questionnaire, a health utilisation questionnaire, and the EQ-5D-5L questionnaire which captures information about a patient’s overall health state. Eligible patients, with continuing consent, will be randomised to the study via the online ATNEC randomisation portal. Patients will be randomised to receive either standard treatment to the armpit (lymph node clearance or radiotherapy to the armpit) or no further armpit treatment. Follow-Up: Patients are required to complete five further questionnaire booklets: at 1 year, 2 years, 3 years, 4 years and 5 years post-randomisation. These questionnaire booklets will be posted directly to patients by Warwick Clinical Trials Unit, to complete at home. Posted questionnaires will include a pre-paid return envelope, so completed questionnaires can be returned to the Warwick Clinical Trials Unit. Beyond the first year, sites will be asked to follow-up patients annually for at least 5 years. Follow-up can be by capturing information from hospital records or by telephone if the treating site has discharged the patient from clinical follow-up. After 5 years, follow-up information will be sought from NHS Digital health records, so long as the patient has given their consent for this. Radiotherapy Quality Assurance Component: The ATNEC trial will have an embedded radiotherapy quality assurance programme, coordinated by the National Radiotherapy Quality Assurance (RTTQA) group. Sites will be required to adhere to the specific radiotherapy planning and delivery guidelines, developed by the RTTQA team. Qualitative Sub-Study: Qualitative research has been embedded within the recruitment phase to identify and investigate recruitment issues and develop effective and realistic strategies to ensure the success of the trial. Participation in any aspect of the qualitative sub-study is optional. Patients who appear eligible for ATNEC will be asked for their permission to audio-record their conversations with their doctor up until the point that they make their decision on whether or not to participate. Prior to any commencement of recording, patients will be given a brief patient information sheet explaining the qualitative sub-study. Patients will be given sufficient time to review this and ask any questions. If patients agree to be recorded, they will be asked to sign a consent form, providing permission for the audio-recordings of their consultations. In addition, patients who were invited to take part in ATNEC (including those who declined to take part) may be invited for interview at a later date to discuss the reasons why they may, or may not, have chosen to take part in the trial. A separate patient information sheet will be provided for this purpose and, should the patient be happy to be interviewed, written informed consent will be obtained. Patients will be asked for their permission to have their interview audio-recorded. This permission is covered in the above-mentioned patient information sheet and informed consent form. It will be made explicitly clear to patients, at the time of their consultation, or following the informed consent process for the trial, that their participation in the qualitative sub-study is completely optional. The decision of patients who decline to take part will be completely respected, and their medical care will not be affected in any way. Researchers who are involved in the ATNEC trial consent process (i.e clinicians and research nurses) will also be invited for an interview. Research staff will also be provided with an information sheet and their informed consent will be required prior to any audio-recording of patient consultations and/or interviews. An overall plan for the qualitative sub-study, including timelines for interviews, is attached to this application. |
| Intervention type | Mixed |
| Primary outcome measure | Co-primary outcomes, collected annually for 5 years: 1. Disease-Free Survival (DFS); defined and calculated as the time from randomisation until the date of the 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 2. Lymphoedema: self-reported based on two items from the validated Lymphoedema and Breast Cancer Questionnaire (LBCQ) (arm “swelling now” and arm “heaviness in the past year”). Lymphoedema will be defined as ‘yes’ to both questions at 5 years. |
| Secondary outcome measures | Collected annually for 5 years: 1. Arm function assessed using the shortened version of the Disability of the Arm, Shoulder and Hand (DASH), the 11-item QuickDASH questionnaire, over 5 years 2. Pain intensity and characteristics measured using questions from the Douleur Neuropathique (DN4) and Pain Numeric Rating Scale (NRS) and will relate to the areas affected by surgery and cancer treatment, over 5 years 3. Axillary recurrence-free interval, calculated from the date of randomisation to the date of axillary recurrence or the censor date. Axillary recurrence is defined as pathologically (cytology or biopsy) and/or radiologically confirmed recurrence in lymph nodes draining the primary tumour site. The date of axillary recurrence is the date on which imaging or pathology report (whichever comes first) confirms axillary recurrence. Axillary recurrence will be compared between the two allocated groups over 5 years 4. Overall survival; calculated as the time from randomisation until the date of death by any cause or the censor date. Overall survival will be compared between the two allocated groups over 5 years 5. Local (breast or chest wall) recurrence is defined as pathologically (cytology or biopsy) and/or radiologically confirmed recurrence after mastectomy in the skin or soft tissue of the chest wall within the anatomical area bounded by the mid-sternal line, the clavicle, the posterior axillary line and the costal margin or any type of breast carcinoma in the breast after conservation therapy. The date of local recurrence is the date on which the imaging or pathology report (whichever comes first) confirms local recurrence. Local recurrence will be compared between the two allocated groups over 5 years 6. Regional (nodal) recurrence is defined as pathologically (cytology or biopsy) and/or radiologically confirmed recurrent tumour in the lymph nodes in the ipsilateral axilla, infraclavicular, supraclavicular fossa, interpectoral area or ipsilateral internal mammary chain. The date of regional recurrence is the date on which the imaging or pathology report (whichever comes first) confirms local recurrence. Regional (nodal) recurrence will be compared between the two allocated groups over 5 years 7. Distant metastasis is defined as confirmed metastasis (positive pathology and/or definitive evidence on imaging) in all other sites of recurrence and may include those classified as: soft-tissue category, visceral category, central nervous system and skeletal spread. The date of distant metastasis is the date on which the imaging or pathology report (whichever comes first) confirms metastasis. Distant metastases will be compared between the two allocated groups over 5 years. 8. Contralateral breast cancer is defined as a new primary malignancy in the opposite breast unless obviously contiguous with recurrent chest wall disease or proven on cytology/biopsy to be of metastatic origin. Contralateral breast cancers will be compared between the two allocated groups over 5 years. 9. Non-breast cancer is defined as any new non-breast primary malignancy, except for basal or squamous cell cancer of the skin, in situ carcinoma of the cervix, or in situ or stage 1 melanoma. New breast cancers will be compared between the two allocated groups over 5 years. 10. Economic evaluation (data to be collected annually, over 5 years, through annual follow-up and patient questionnaires): 10.1. Costs to the NHS and participants will be compared between the two allocated groups over 5 years 10.2. Quality-adjusted life years (QALYs) will be compared between the two groups over 5 years. QALYs based on responses to the EQ-5D-5L administered at baseline, 12, 24, 36, 48, and 60 months post-randomisation 10.3. Incremental cost per disease-free interval over 5 years 10.4. Incremental cost per lymphoedema avoided over 5 years 10.5. Incremental cost per QALY gained over 5 years 10.6. Incremental cost per QALY over the estimated lifetime of a participant with early-stage breast cancer |
| Overall study start date | 01/03/2020 |
| Overall study end date | 01/03/2030 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 1900; UK Sample Size: 1900 |
| Participant inclusion criteria | Current inclusion criteria as of 05/02/2024: 1. Age ≥18 years 2. Male or female 3. cT1-3N1M0 breast cancer at diagnosis (prior to NACT) as per AJCC 8th edition 3.2 Patients with occult primary invasive breast cancer (no identifiable invasive cancer in the breast) with FNA or core biopsy provide nodal metastases are also eligible for the study. 4. FNA or core biopsy confirmed axillary nodal metastases at presentation 5. Oestrogen receptor and HER2 status evaluated on primary tumour 6. Received standard NACT as per local guidelines (Patients undergoing neoadjuvant endocrine therapy as part of another clinical trial are eligible) 7. Imaging of the axilla, as required, to assess response to NACT (per local guidelines) 8. Undergo a dual tracer sentinel node biopsy (SNB) after NACT with at least 3 nodes removed in total (sentinel nodes and marked node). 8.1 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. 8.2 If the node is not marked, or marked node is not removed: the patient is eligible only if the histology report shows evidence of downstaging with complete pathological response e.g. fibrosis or scarring in at least one node and at least 3 nodes removed. 8.3 If fewer than 3 nodes are found on histology: the patient is eligible only if BOTH points a) and b), below, are met: a) involved node was marked and removed during SNB; and b) removed marked node shows evidence of downstaging on histology e.g. fibrosis or scarring. 8.4 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 (including the marked node). 9. No evidence of nodal metastases post NACT (isolated tumour cells, micro or macrometastasis) _____ Previous inclusion criteria as of 19/07/2023 to 05/02/2024: 1. Age ≥18 years 2. Male or female 3. cT1-3N1M0 breast cancer at diagnosis (prior to NACT) as per AJCC 8th edition 4. FNA or core biopsy confirmed axillary nodal metastases at presentation 5. Oestrogen receptor, progesterone receptor and HER2 status evaluated on primary tumour 6. Received standard NACT as per local guidelines (Patients undergoing neoadjuvant endocrine therapy as part of another clinical trial are eligible) 7. Imaging of the axilla to assess response to NACT (as per local guidelines) 8. Undergo dual tracer sentinel node biopsy after NACT and at least 3 nodes removed (sentinel nodes and marked node). 8.1 If a single tracer is used, the patient will be eligible if the involved node is marked before or during NACT, and the marked node and at least 3 nodes (including the marked node) are removed during sentinel node biopsy. 8.2 If axillary node sampling is performed following failed localisation of sentinel nodes, patient will be eligible if at least three nodes removed (including the marked node). 8.3 If node is not marked, or marked node is not removed, the patient will be eligible if the histology report shows evidence of downstaging with complete pathological response e.g. fibrosis or scarring in at least one node and at least 3 nodes removed. 8.4 If fewer than 3 nodes are found on histology, the patient is eligible if: a) involved node was marked and removed during SNB; and b) removed marked node shows evidence of downstaging on histology e.g. fibrosis or scarring. 9. No evidence of nodal metastases post NACT (isolated tumour cells, micro or macrometastasis) _____ Previous inclusion criteria: 1. Age ≥18 years 2. Male or female 3. T1-3N1M0 breast cancer at diagnosis (prior to NACT) 4. FNA or core biopsy confirmed axillary nodal metastases at presentation 5. Oestrogen receptor, progesterone receptor and HER2 status evaluated on primary tumour 6. Received standard NACT as per local guidelines (Patients undergoing neoadjuvant endocrine therapy as part of another clinical trial are eligible) 7. Ultrasound of the axilla at completion of NACT 8. Undergo dual tracer sentinel node biopsy after NACT and at least 3 nodes removed (sentinel nodes and marked node). If axillary node sampling is performed following failed localisation of sentinel nodes, patient will be eligible if at least three nodes removed (including the marked node) 9. No evidence of nodal metastases post NACT (isolated tumour cells, micro or macrometastasis) |
| Participant exclusion criteria | Current exclusion criteria as of 19/07/2023: 1. Bilateral synchronous invasive breast cancer 2. Sentinel node biopsy prior to NACT 3. Previous axillary surgery on the same body side as the scheduled targeted sampling 4. Any previous cancer within 5 years or concomitant malignancy except: 4.1. Basal or squamous cell carcinoma of the skin 4.2. In situ carcinoma of the cervix 4.3. In situ melanoma 4.4. Contra- or ipsilateral in situ breast cancer _____ Previous exclusion criteria: 1. Bilateral invasive breast cancer 2. Sentinel node biopsy prior to NACT 3. Marked node not removed except where the node/s removed show evidence of down-staging with complete pathological response e.g. fibrosis or scarring 4. Previous axillary surgery on the same body side as the scheduled targeted sampling 5. Any previous cancer within 5 years or concomitant malignancy except: 5.1. Basal or squamous cell carcinoma of the skin 5.2. In situ carcinoma of the cervix 5.3. In situ melanoma 5.4. Contra- or ipsilateral in situ breast cancer |
| Recruitment start date | 21/12/2020 |
| Recruitment end date | 01/03/2026 |
Locations
Countries of recruitment
- England
- Isle of Man
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
2 Eday Road
ABERDEEN
AB15 6RE
United Kingdom
HILLS ROAD
CAMBRIDGE
CB2 0QQ
United Kingdom
FRIMLEY
CAMBERLEY
GU16 7UJ
United Kingdom
Gartnavel Royal Hospital
1055 Great Western Road
Glasgow
G12 0XH
United Kingdom
Stirling
FK8 1DX
United Kingdom
10 Arthur Street
AYR
KA7 1QJ
United Kingdom
A Floor - Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom
MELROSE
TD6 9DB
United Kingdom
SOUTHMEAD ROAD
WESTBURY-ON-TRYM
BRISTOL
BS10 5NB
United Kingdom
369 FULHAM ROAD
LONDON
SW10 9NH
United Kingdom
UNION WALK
HEREFORD
HR1 2ER
United Kingdom
HEADLEY WAY
HEADINGTON
OXFORD
OX3 9DU
United Kingdom
Prescot Street
Liverpool
L7 8XP
United Kingdom
WARRINGTON ROAD
PRESCOT
L35 5DR
United Kingdom
Derriford Road
PLYMOUTH
PL6 8DH
United Kingdom
FREEMAN ROAD
HIGH HEATON
NEWCASTLE-UPON-TYNE
NE7 7DN
United Kingdom
HOLDFORTH ROAD
HARTLEPOOL
CLEVELAND
TS24 9AH
United Kingdom
INFIRMARY SQUARE
LEICESTER
LE1 5WW
United Kingdom
GREETWELL ROAD
LINCOLN
LN2 5QY
United Kingdom
WATFORD GENERAL HOSPITAL
VICARAGE ROAD
WATFORD
WD18 0HB
United Kingdom
Lydeard House
Musgrove Park Hospital
Taunton
TA1 5DA
United Kingdom
17 Old Edinburgh Road
INVERNESS
IV2 3HG
United Kingdom
TRELISKE
TRURO
TR1 3LJ
United Kingdom
UTTOXETER ROAD
DERBY
DE22 3NE
United Kingdom
POND STREET
LONDON
NW3 2QG
United Kingdom
Westcliff-on-sea
SS0 0RY
United Kingdom
BURTON ROAD
KENDAL
LA9 7RG
United Kingdom
STOKE-ON-TRENT
ST4 6QG
United Kingdom
EASTERN ROAD
BRIGHTON
BN2 5BE
United Kingdom
Jobs Well Road
Carmarthen
SA31 3BB
United Kingdom
GUILDFORD ROAD
CHERTSEY
KT16 0PZ
United Kingdom
Skipton Road
Steeton
Keighley
BD20 6TD
United Kingdom
ABERFORD ROAD
WAKEFIELD
WF1 4DG
United Kingdom
ACRE STREET
HUDDERSFIELD
HD3 3EA
United Kingdom
ROYAL ALBERT EDWARD INFIRMARY
WIGAN LANE
WIGAN
WN1 2NN
United Kingdom
MINERVA ROAD
FARNWORTH
BOLTON
BL4 0JR
United Kingdom
DISTRICT GEN HOSPITAL
VICTORIA ROAD
MACCLESFIELD
SK10 3BL
United Kingdom
OXFORD ROAD
MANCHESTER
M13 9WL
United Kingdom
MARTON ROAD
MIDDLESBROUGH
CLEVELAND
TS4 3BW
United Kingdom
LONDON
NW1 2PG
United Kingdom
HAMILTON
ML3 0TA
United Kingdom
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
ROTHERHAM
S60 2UD
United Kingdom
ARMTHORPE ROAD
DONCASTER
DN2 5LT
United Kingdom
HERRIES ROAD
SHEFFIELD
S5 7AU
United Kingdom
LONDON ROAD
READING
RG1 5AN
United Kingdom
MINDELSOHN WAY
EDGBASTON
BIRMINGHAM
B15 2GW
United Kingdom
LUTON
LU4 0DZ
United Kingdom
HOSPITAL
BARRACK ROAD
EXETER
EX2 5DW
United Kingdom
DUDLEY ROAD
BIRMINGHAM
B18 7QH
United Kingdom
LONDON
SW3 6JJ
United Kingdom
STERLING WAY
LONDON
N18 1QX
United Kingdom
PORTLAND PLACE
PENRITH
CA11 7BF
United Kingdom
Haslingden Road
Blackburn
BB2 3HH
United Kingdom
Anlaby Road
Hull
HU3 2JZ
United Kingdom
St Marys Hospital
South Wharf Road
London
W2 1BL
United Kingdom
Arrowe Park Road
Upton
Wirral
CH49 5PE
United Kingdom
Liverpool Road
Chester
CH2 1UL
United Kingdom
Hollyhurst Road
Darlington
DL3 6HX
United Kingdom
The Crichton
Bankend Road
Dumfries
DG1 4ZG
United Kingdom
Gorleston
Great Yarmouth
NR31 6LA
United Kingdom
Denmark Hill
London
SE5 9RS
United Kingdom
Leighton
Crewe
CW1 4QJ
United Kingdom
Eaglestone
Milton Keynes
MK6 5LD
United Kingdom
Wolverhampton Road
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Sheriff Hill
Gateshead
NE9 6SX
United Kingdom
Hayfield Road
Kirkcaldy
KY2 5AH
United Kingdom
Shrewsbury
SY3 8XQ
United Kingdom
Beckett Street
Leeds
LS9 7TF
United Kingdom
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom
Fountain Street
Ashton-under-lyne
OL6 9RW
United Kingdom
Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom
Whielden Street
Amersham
HP7 0JD
United Kingdom
Wigginton Road
York
YO31 8HE
United Kingdom
Sponsor information
Hospital/treatment centre
c/o Teresa Grieve
Royal Derby Hospital
Uttoxeter Road
Derby
DE22 3NE
England
United Kingdom
| Phone | +44 (0)1332 724639 |
|---|---|
| teresa.grieve@nhs.net |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/03/2031 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 1. The researchers intend to publish the protocol in an open-access journal. 2. Planned publication in a high-impact peer-reviewed journal. Publication of the results will be based on outcomes at least 5 years following the last recruited participant. No interim publication of results is planned at present. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request. Participant data is stored on a secure server at WCTU where each participant has been assigned a de-identified trial number. Any requests for access to the trial data should be sent to the CI who will inform the data custodians and agreement will be made through the data access committee which will comprise of the principal investigators from the trial management group. For each data sharing request, it is essential that a proforma is completed which will describe the purpose, scope, data items requested, analysis plan and acknowledgment of the trial management team. Requestors who are granted access to the data will be required to complete a data-sharing agreement which will be signed by the requester, sponsor and principal investigator(s). The researchers anticipate that data sharing will be possible after the publication of the primary endpoint of the trial. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
05/02/2024: The participant inclusion criteria were changed.
19/07/2023: The following changes were made to the trial record:
1. The interventions were changed.
2. The inclusion criteria were changed.
3. The exclusion criteria were changed.
4. The study participating centres HAMPSHIRE HOSPITALS NHS FOUNDATION TRUST, NORTHERN LINCOLNSHIRE AND GOOLE NHS FOUNDATION TRUST, Noble's Hospital, DORSET COUNTY HOSPITAL NHS FOUNDATION TRUST, MEDWAY NHS FOUNDATION TRUST, BETSI CADWALADR UNIVERSITY LHB, KETTERING GENERAL HOSPITAL NHS FOUNDATION TRUST, ST GEORGE'S UNIVERSITY HOSPITALS NHS FOUNDATION TRUST, SWANSEA BAY UNIVERSITY LOCAL HEALTH BOARD, PENNINE ACUTE HOSPITALS NHS TRUST, CARDIFF & VALE UNIVERSITY LHB, WORCESTERSHIRE ACUTE HOSPITALS NHS TRUST, NOTTINGHAM UNIVERSITY HOSPITALS NHS TRUST, SHERWOOD FOREST HOSPITALS NHS FOUNDATION TRUST, WEST SUFFOLK NHS FOUNDATION TRUST, ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST, TAUNTON AND SOMERSET NHS FOUNDATION TRUST, BASILDON AND THURROCK UNIVERSITY HOSPITALS NHS FOUNDATION TRUST, HYWEL DDA UNIVERSITY LHB, SOUTHEND UNIVERSITY HOSPITAL NHS FOUNDATION TRUST were removed.
5. The study participating centres Liverpool University Hospitals NHS Foundation Trust, Somerset NHS Foundation Trust, Mid and South Essex NHS Foundation Trust, Hywel Dda NHS Trust, Airedale NHS Foundation Trust, East Lancashire Hospitals NHS Trust, Hull University Teaching Hospitals NHS Trust, Imperial College Healthcare NHS Trust, Wirral University Teaching Hospital NHS Foundation Trust, Countess of Chester Hospital NHS Foundation Trust, County Durham and Darlington NHS Foundation Trust, NHS Dumfries and Galloway, James Paget University Hospitals NHS Foundation Trust, King's College Hospital NHS Foundation Trust, Mid Cheshire Hospitals NHS Foundation Trust, Milton Keynes University Hospital NHS Foundation Trust, The Royal Wolverhampton NHS Trust, Gateshead Health NHS Foundation Trust, NHS Fife, The Shrewsbury and Telford Hospital NHS Trust, Leeds Teaching Hospitals NHS Trust, Bradford Teaching Hospitals NHS Foundation Trust, Tameside and Glossop Integrated Care NHS Foundation Trust, The Clatterbridge Cancer Centre NHS Foundation Trust, Buckinghamshire Healthcare NHS Trust and York and Scarborough Teaching Hospitals NHS Foundation Trust were added.
13/04/2021: Cancer Research UK lay summary link added to plain English summary field.
05/02/2021: The recruitment start date was changed from 01/03/2021 to 21/12/2020.
27/10/2020: Trial's existence confirmed by the NIHR.
