Trial of Perioperative Endocrine Therapy - Individualising Care
- Conditions
- Breast Cancer
- Interventions
- Drug: Aromatase Inhibitors
- Registration Number
- NCT02338310
- Lead Sponsor
- Institute of Cancer Research, United Kingdom
- Brief Summary
To determine whether perioperative endocrine therapy with an aromatase inhibitor (AI) followed by standard adjuvant therapy improves outcome compared with standard adjuvant therapy alone in postmenopausal women with hormone receptor positive breast cancer.
To determine whether the proliferation marker Ki67 as measured by immunohistochemistry (IHC) in the excised cancer around 2 weeks after starting AI therapy will predict for time to recurrence (TTR) in the individual patient more effectively than the pre-treatment Ki67 value.
To determine whether molecular profiling 2 weeks after starting endocrine therapy predicts for long-term outcome in postmenopausal women with hormone receptor positive breast cancer better than at diagnosis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 4486
-
Post menopausal women with core biopsy-proven hormone receptor positive invasive breast cancer. Postmenopausal is defined as a woman aged ≥50 years fulfilling any one of the following criteria:
i) with amenorrhoea >12 months and an intact uterus; ii) has undergone a bilateral oophorectomy; iii) in women who have undergone a hysterectomy, then FSH levels within the postmenopausal range (utilising ranges from the testing laboratory facility) are required if the patient is aged <55 years; or iv) in women who have been on HRT within the last 12 months and therefore not amenorrhoeic, FSH levels within the postmenopausal range (utilising ranges from the testing laboratory facility) are required if the patient is aged <55 years.
-
No evidence of metastatic spread by standard assessment according to local guidelines
-
Standard adjuvant endocrine therapy indicated
-
A palpable tumour of any size , or a tumour with an ultrasound size of at least 1.5cm
-
WHO performance status of 0 or 1
-
Written informed consent to participate in the trial and to donation of tissue (fresh tissue and surplus tissue from diagnostic procedures) and blood samples.
- Locally advanced/inoperable breast cancer
- Evidence of metastatic disease
- Previous invasive breast cancer (surgically treated DCIS or LCIS allowed)
- Current bilateral breast cancer
- Multiple unilateral tumours with different ER/PgR/HER2 status, grade or type (e.g. ductal vs lobular) i.e. anything that suggests two or more different cancers. Multifocal disease with homogenous ER/PgR/HER2 status, grade and type is allowed if at least one lesion is palpable or at least 1.5cm on ultrasound; the largest lesion should be used for sample collection and CRF completion.
- Concurrent use (defined as use within 4 weeks prior to diagnostic tissue sample being taken) of HRT or any other oestrogen-containing medication (including vaginal oestrogens)
- Previous use of oestrogen implants at ANY time
- Prior endocrine therapy or chemotherapy for breast cancer
- Any invasive malignancy diagnosed within previous 5 years (other than basal cell carcinoma or cervical carcinoma in situ)
- Any severe co-incident medical disease, inability to give informed consent or unavailability for follow-up
- Treatment with an unlicensed or investigational drug within 4 weeks before randomisation
- Current, continuous, long term systemic steroid usage
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aromatase Inhibitor Aromatase Inhibitors Aromatase Inhibitor given perioperatively for 4 weeks (two weeks before and two weeks after surgery) Choice of AI is according to centre policy and may be either anastrozole (1mg/day) or letrozole (2.5mg/day)
- Primary Outcome Measures
Name Time Method Time to recurrence 5 years post-randomisation Time to recurrence (TTR) is defined as time from randomisation to local, regional, or distant tumour recurrence or death from breast cancer without prior notification of relapse. Second primary cancers and intercurrent deaths will be treated as censoring events. Patients who are alive and disease free will be censored at the date last seen alive.
- Secondary Outcome Measures
Name Time Method Relapse free survival 5 years post-randomisation Second primary cancers and deaths from non-breast cancer causes in the absence of breast cancer relapse will be treated as censoring events.
Time to local recurrence 5 years post-randomisation Time to distant recurrence 5 years post-randomisation Overall Survival 5 years post-randomisation Breast cancer free survival 5 years post-randomisation Proliferation rate (Ki67) At time of surgery (around 2 weeks post-randomisation) Comparison of the predictive value of Ki67 at surgery in the perioperative therapy and non perioperative therapy groups will be undertaken using Cox regression, comparing the estimates of the hazard ratios obtained in each treatment group.
Gene expression profile At time of surgery (around 2 weeks post-randomisation)
Trial Locations
- Locations (127)
Tunbridge Wells Hospital
🇬🇧Tunbridge Wells, Kent, United Kingdom
Medway Maritime Hospital
🇬🇧Gillingham, Kent, United Kingdom
Stoke Mandeville Hospital
🇬🇧Aylesbury, Buckinghamshire, United Kingdom
East Surrey Hospital
🇬🇧Redhill, Surrey, United Kingdom
Royal Marsden Hosital,
🇬🇧Sutton, England, United Kingdom
Bronglais District General Hospital
🇬🇧Aberystwyth, Wales, United Kingdom
Burnley General Hospital
🇬🇧Burnley, England, United Kingdom
Cumberland Infirmary
🇬🇧Carlisle, England, United Kingdom
Countess of Chester Hospital
🇬🇧Chester, England, United Kingdom
Chelmsford and Essex Centre
🇬🇧Chelmsford, England, United Kingdom
Prince Philip Hospital
🇬🇧Llanelli, Carmarthenshire, United Kingdom
Queen Elizabeth II Hospital
🇬🇧Welwyn Garden City, Hertfordshire, United Kingdom
Grantham and District Hospital
🇬🇧Grantham, Lincolnshire, United Kingdom
Princess Royal Hospital
🇬🇧Telford, Shropshire, United Kingdom
North Devon District Hospital
🇬🇧Barnstaple, England, United Kingdom
Doncaster Royal Infirmary
🇬🇧Doncaster, England, United Kingdom
Royal Marsden - London
🇬🇧London, England, United Kingdom
North Tyneside Hospital
🇬🇧North Shields, England, United Kingdom
Singleton Hospital
🇬🇧Swansea, Wales, United Kingdom
Ulster Hospital
🇬🇧Dundonald, Belfast, United Kingdom
Wansbeck General Hospital
🇬🇧Ashington, England, United Kingdom
City Hospital - Birmingham
🇬🇧Birmingham, England, United Kingdom
Whittington Hospital
🇬🇧London, England, United Kingdom
Kidderminster Hospital
🇬🇧Kidderminster, England, United Kingdom
North Manchester General Hospital - Penine Actute Hospitals Trust
🇬🇧Manchester, England, United Kingdom
King's College Hospital
🇬🇧London, England, United Kingdom
St Albans City Hospital
🇬🇧St Albans, Hertfordshire, United Kingdom
Weston General Hospital, Avon
🇬🇧Weston-Super-Mare, Somerset, United Kingdom
Royal Berkshire Hospital
🇬🇧Reading, England, United Kingdom
Southend NHS Trust Hospital
🇬🇧Westcliff-On-Sea, England, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle, Newcastle-Upon-Tyne, United Kingdom
Pilgrim Hospital
🇬🇧Boston, England, United Kingdom
Bradford Teaching Hospitals NHS Trust, St Luke's Hospital
🇬🇧Bradford, England, United Kingdom
Royal Free Hospital
🇬🇧London, England, United Kingdom
Northampton General Hospital NHS Trust
🇬🇧Northampton, England, United Kingdom
University Hospital of North Staffordshire
🇬🇧Stoke-On-Trent, England, United Kingdom
St Margaret's Hospital
🇬🇧Epping, Essex, United Kingdom
Princess Royal University Hospital
🇬🇧Orpington, Kent, United Kingdom
Harrogate District Hospital
🇬🇧Harrogate, North Yorkshire, United Kingdom
Cheltenham General Hospital
🇬🇧Gloucester, Gloucs, United Kingdom
Wythenshawe Hospital
🇬🇧Manchester, England, United Kingdom
Barnsley District General Hospital
🇬🇧Barnsley, South Yorkshire, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, Scotland, United Kingdom
Ealing Hospital
🇬🇧Southall, Middlesex, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, England, United Kingdom
Belfast City Hospital
🇬🇧Belfast, Northern Ireland, United Kingdom
University Hospital, Lewisham
🇬🇧Lewisham, London, United Kingdom
Rotherham District General Hospital
🇬🇧Rotherham, South Yorkshire, United Kingdom
Withybush General Hospital
🇬🇧Haverfordwest, Wales, United Kingdom
Royal Bolton Hospital
🇬🇧Bolton, United Kingdom
Leighton Hospital
🇬🇧Crewe, United Kingdom
Ysbyty Gwynedd
🇬🇧Bangor, United Kingdom
Kingston Hospital
🇬🇧Kingston Upon Thames, Surrey, United Kingdom
University Hospital Coventry
🇬🇧Coventry, United Kingdom
Royal United Hospital
🇬🇧Bath, United Kingdom
Darent Valley Hospital
🇬🇧Dartford, United Kingdom
East Kent Hospitals
🇬🇧Canterbury, United Kingdom
Homerton University Hospital
🇬🇧London, United Kingdom
Hereford County Hospital
🇬🇧Hereford, United Kingdom
Northwick Park Hospital
🇬🇧London, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
Leeds General Infirmary/ St James' University Hospital
🇬🇧Leeds, United Kingdom
Lincoln County Hospital
🇬🇧Lincoln, United Kingdom
Queen's Hospital,
🇬🇧Romford, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Staffordshire General Hospital
🇬🇧Stafford, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Torbay District General Hospital
🇬🇧Torquay, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Mid Yorkshire Hospitals
🇬🇧Wakefield, United Kingdom
Royal Bournemouth General Hospital
🇬🇧Bournemouth, United Kingdom
Bristol Royal Infirmary
🇬🇧Bristol, United Kingdom
Southmead Hospital
🇬🇧Bristol, United Kingdom
Western Infirmary
🇬🇧Glasgow, United Kingdom
Frimley Park Hospital
🇬🇧Frimley, United Kingdom
Royal Surrey County Hospital
🇬🇧Guildford, United Kingdom
Ipswich Hospital
🇬🇧Ipswich, United Kingdom
St Bartholomew's Hospital
🇬🇧London, United Kingdom
Luton and Dunstable Hospital
🇬🇧Luton, United Kingdom
Hillingdon Hospital
🇬🇧Middlesex, United Kingdom
Milton Keynes General Hospital
🇬🇧Milton Keynes, United Kingdom
Salford Royal Hospital
🇬🇧Salford, United Kingdom
Dorset County Hospital
🇬🇧Poole, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom
Stepping Hill Hospital
🇬🇧Stockport, United Kingdom
St George's Hospital,
🇬🇧Tooting, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
Royal Albert Edward Infirmary
🇬🇧Wigan, United Kingdom
Worthing Hospital
🇬🇧Worthing, United Kingdom
Heatherwood and Wexham Park Hospitals NHS trust
🇬🇧Slough, Berkshire, United Kingdom
Craigavon Area Hospital
🇬🇧Portadown, Co.Amagh, United Kingdom
Chesterfield Royal Hospital
🇬🇧Chesterfield, England, United Kingdom
Poole Hospital
🇬🇧Poole Dorset, England, United Kingdom
Royal Hampshire County Hospital
🇬🇧Winchester, England, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Dumfries & Galloway Royal Infirmary
🇬🇧Dumfries, Scotland, United Kingdom
Ashford and St Peter's Hospitals
🇬🇧Chertsey, Surrey, United Kingdom
Tameside General Hospital
🇬🇧Ashton-Under-Lyne, United Kingdom
Neath Port Talbot Hospital
🇬🇧Port Talbot, West Glamorgan, United Kingdom
University Hospital Of Wales
🇬🇧Cardiff, United Kingdom
Royal Derby Hospital
🇬🇧Derby, United Kingdom
Huddersfield Royal Infirmary
🇬🇧Huddersfield, United Kingdom
Norfolk and Norwich University Hospital
🇬🇧Norwich, United Kingdom
Macclesfield District General Hospital
🇬🇧Macclesfield, United Kingdom
University Hospitals of Leicester NHS Trust
🇬🇧Leicester, United Kingdom
Maidstone Hospital
🇬🇧Maidstone, United Kingdom
Salisbury District Hospital
🇬🇧Salisbury, United Kingdom
University Hospital of North Tees
🇬🇧Stockton-on-Tees, United Kingdom
Musgrove Park Hospital
🇬🇧Taunton, United Kingdom
Warwick Hospital
🇬🇧Warwick, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
St. Mary's Hospital
🇬🇧London, England, United Kingdom
Royal Blackburn Hospital
🇬🇧Blackburn, England, United Kingdom
Essex County Hospital
🇬🇧Colchester, England, United Kingdom
Russells Hall Hospital
🇬🇧Dudley, England, United Kingdom
Wycombe General Hospital
🇬🇧High Wycombe, England, United Kingdom
Airedale General Hospital
🇬🇧Keighley, England, United Kingdom
George Eliot Hospital
🇬🇧Nuneaton, England, United Kingdom
Royal Oldham Hospital
🇬🇧Oldham, England, United Kingdom
Worcester Royal Hospital
🇬🇧Worcester, England, United Kingdom
Yeovil District Hospital
🇬🇧Yeovil, England, United Kingdom
Ninewells Hospital
🇬🇧Dundee, Scotland, United Kingdom
North Wales CTC, Glan Clwyd Hospital
🇬🇧Rhyl, Wales, United Kingdom
Guy's Hospital
🇬🇧London, England, United Kingdom
Castle Hill Hospital
🇬🇧Cottingham, United Kingdom
Charing Cross Hospital
🇬🇧London, United Kingdom
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom