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| ID | Type | Description | Link |
|---|---|---|---|
| 2007-003877-21 | EudraCT Number | ||
| CRUK/07/015 | Other Grant/Funding Number | Cancer Research UK | |
| 08/H1102/37 | Other Identifier | Main Research Ethics Committee Number | |
| 63882543 | Registry Identifier | ISRCTN | |
| CCR 2973 | Other Identifier | Sponsor |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| No Aromatase Inhibitor | No Intervention | No aromatase inhibitor given around the time of surgery | |
| Aromatase Inhibitor | Experimental | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aromatase Inhibitors | Drug | Choice of AI is according to centre policy; any brand can be used |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to recurrence | 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. | 5 years post-randomisation |
| Measure | Description | Time Frame |
|---|---|---|
| Relapse free survival | Second primary cancers and deaths from non-breast cancer causes in the absence of breast cancer relapse will be treated as censoring events. | 5 years post-randomisation |
| Time to local recurrence |
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Inclusion Criteria:
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.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ian Smith, Professor | Royal Marsden NHS Foundation Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ulster Hospital | Dundonald | Belfast | BT16 1RH | United Kingdom | ||
| Heatherwood and Wexham Park Hospitals NHS trust |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33152284 | Derived | Smith I, Robertson J, Kilburn L, Wilcox M, Evans A, Holcombe C, Horgan K, Kirwan C, Mallon E, Sibbering M, Skene A, Vidya R, Cheang M, Banerji J, Morden J, Sidhu K, Dodson A, Bliss JM, Dowsett M. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020 Nov;21(11):1443-1454. doi: 10.1016/S1470-2045(20)30458-7. |
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| 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) | 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. | At time of surgery (around 2 weeks post-randomisation) |
| Gene expression profile | At time of surgery (around 2 weeks post-randomisation) |
| Slough |
| Berkshire |
| SL2 4HL |
| United Kingdom |
| Stoke Mandeville Hospital | Aylesbury | Buckinghamshire | HP21 8AL | United Kingdom |
| Prince Philip Hospital | Llanelli | Carmarthenshire | SA14 8QF | United Kingdom |
| Craigavon Area Hospital | Portadown | Co.Amagh | BT63 5QQ | United Kingdom |
| Wansbeck General Hospital | Ashington | England | NE63 9JJ | United Kingdom |
| North Devon District Hospital | Barnstaple | England | EX31 4JB | United Kingdom |
| City Hospital - Birmingham | Birmingham | England | B18 7QH | United Kingdom |
| Royal Blackburn Hospital | Blackburn | England | BB2 3HH | United Kingdom |
| Pilgrim Hospital | Boston | England | PE21 9QT | United Kingdom |
| Bradford Teaching Hospitals NHS Trust, St Luke's Hospital | Bradford | England | BD5 0NA | United Kingdom |
| Burnley General Hospital | Burnley | England | BB10 2PQ | United Kingdom |
| Cumberland Infirmary | Carlisle | England | CA2 7HY | United Kingdom |
| Chelmsford and Essex Centre | Chelmsford | England | CM2 0QH | United Kingdom |
| Countess of Chester Hospital | Chester | England | CH2 1UL | United Kingdom |
| Chesterfield Royal Hospital | Chesterfield | England | S44 5BL | United Kingdom |
| Essex County Hospital | Colchester | England | C03 3NB | United Kingdom |
| Doncaster Royal Infirmary | Doncaster | England | DN2 5LT | United Kingdom |
| Russells Hall Hospital | Dudley | England | DY1 2HQ | United Kingdom |
| Wycombe General Hospital | High Wycombe | England | United Kingdom |
| Airedale General Hospital | Keighley | England | BD20 6TD | United Kingdom |
| Kidderminster Hospital | Kidderminster | England | DY11 6RJ | United Kingdom |
| Whittington Hospital | London | England | N19 5NF | United Kingdom |
| Royal Free Hospital | London | England | NW3 2QG | United Kingdom |
| Guy's Hospital | London | England | SE1 9RT | United Kingdom |
| King's College Hospital | London | England | SE5 9RS | United Kingdom |
| Royal Marsden - London | London | England | SW3 6JJ | United Kingdom |
| St. Mary's Hospital | London | England | W2 1NY | United Kingdom |
| Wythenshawe Hospital | Manchester | England | M23 9LJ | United Kingdom |
| North Manchester General Hospital - Penine Actute Hospitals Trust | Manchester | England | M8 6RB | United Kingdom |
| North Tyneside Hospital | North Shields | England | NE29 8NH | United Kingdom |
| Northampton General Hospital NHS Trust | Northampton | England | NN6 8BJ | United Kingdom |
| George Eliot Hospital | Nuneaton | England | CV10 7DJ | United Kingdom |
| Royal Oldham Hospital | Oldham | England | OL1 2JH | United Kingdom |
| Poole Hospital | Poole Dorset | England | BH15 2JB | United Kingdom |
| Royal Berkshire Hospital | Reading | England | RG1 5AN | United Kingdom |
| University Hospital of North Staffordshire | Stoke-on-Trent | England | ST4 7LN | United Kingdom |
| Royal Marsden Hosital, | Sutton | England | SM2 5PT | United Kingdom |
| Southend NHS Trust Hospital | Westcliff-on-Sea | England | SS0 0RY | United Kingdom |
| Royal Hampshire County Hospital | Winchester | England | SO22 5DG | United Kingdom |
| New Cross Hospital | Wolverhampton | England | WV10 0QP | United Kingdom |
| Worcester Royal Hospital | Worcester | England | WR5 1DD | United Kingdom |
| Yeovil District Hospital | Yeovil | England | BA21 4AT | United Kingdom |
| St Margaret's Hospital | Epping | Essex | CM16 6TN | United Kingdom |
| Cheltenham General Hospital | Gloucester | Gloucs | United Kingdom |
| St Albans City Hospital | St Albans | Hertfordshire | AL3 5PN | United Kingdom |
| Queen Elizabeth II Hospital | Welwyn Garden City | Hertfordshire | AL7 4HQ | United Kingdom |
| Medway Maritime Hospital | Gillingham | Kent | ME7 5NY | United Kingdom |
| Princess Royal University Hospital | Orpington | Kent | BR6 8ND | United Kingdom |
| Tunbridge Wells Hospital | Royal Tunbridge Wells | Kent | TN2 4QL | United Kingdom |
| Grantham and District Hospital | Grantham | Lincolnshire | NG31 8DG | United Kingdom |
| University Hospital, Lewisham | Lewisham | London | SE13 6LH | United Kingdom |
| Queen Elizabeth Hospital | Woolwich | London | SE18 4QH | United Kingdom |
| Ealing Hospital | Southall | Middlesex | UB1 3HW | United Kingdom |
| Royal Victoria Infirmary | Newcastle | Newcastle-Upon-Tyne | NE1 4LP | United Kingdom |
| Harrogate District Hospital | Harrogate | North Yorkshire | HG2 7SX | United Kingdom |
| Belfast City Hospital | Belfast | Northern Ireland | BT9 7AB | United Kingdom |
| Aberdeen Royal Infirmary | Aberdeen | Scotland | AB25 2ZN | United Kingdom |
| Dumfries & Galloway Royal Infirmary | Dumfries | Scotland | DG1 4AP | United Kingdom |
| Ninewells Hospital | Dundee | Scotland | DD1 9SY | United Kingdom |
| Princess Royal Hospital | Telford | Shropshire | TF1 6TF | United Kingdom |
| Weston General Hospital, Avon | Weston-super-Mare | Somerset | BS23 4TQ | United Kingdom |
| Barnsley District General Hospital | Barnsley | South Yorkshire | S75 2EP | United Kingdom |
| Rotherham District General Hospital | Rotherham | South Yorkshire | S60 2UD | United Kingdom |
| Ashford and St Peter's Hospitals | Chertsey | Surrey | KT16 0PZ | United Kingdom |
| Kingston Hospital | Kingston upon Thames | Surrey | KT2 7QB | United Kingdom |
| East Surrey Hospital | Redhill | Surrey | RH1 5RH | United Kingdom |
| Bronglais District General Hospital | Aberystwyth | Wales | SY23 1ER | United Kingdom |
| Withybush General Hospital | Haverfordwest | Wales | SA61 2PZ | United Kingdom |
| North Wales CTC, Glan Clwyd Hospital | Rhyl | Wales | LL18 5UJ | United Kingdom |
| Singleton Hospital | Swansea | Wales | SA 2 8QA | United Kingdom |
| Neath Port Talbot Hospital | Port Talbot | West Glamorgan | SA12 7BX | United Kingdom |
| Tameside General Hospital | Ashton-under-Lyne | United Kingdom |
| Ysbyty Gwynedd | Bangor | United Kingdom |
| Royal United Hospital | Bath | United Kingdom |
| Queen Elizabeth Hospital | Birmingham | United Kingdom |
| Royal Bolton Hospital | Bolton | United Kingdom |
| Royal Bournemouth General Hospital | Bournemouth | United Kingdom |
| Bristol Royal Infirmary | Bristol | United Kingdom |
| Southmead Hospital | Bristol | United Kingdom |
| Addenbrooke's Hospital | Cambridge | United Kingdom |
| East Kent Hospitals | Canterbury | United Kingdom |
| University Hospital Of Wales | Cardiff | United Kingdom |
| Castle Hill Hospital | Cottingham | United Kingdom |
| University Hospital Coventry | Coventry | CV2 2DX | United Kingdom |
| Leighton Hospital | Crewe | United Kingdom |
| Darent Valley Hospital | Dartford | United Kingdom |
| Royal Derby Hospital | Derby | United Kingdom |
| Royal Devon and Exeter Hospital | Exeter | United Kingdom |
| Frimley Park Hospital | Frimley | United Kingdom |
| Western Infirmary | Glasgow | G11 6NT | United Kingdom |
| Royal Surrey County Hospital | Guildford | United Kingdom |
| Hereford County Hospital | Hereford | HR1 2ER | United Kingdom |
| Huddersfield Royal Infirmary | Huddersfield | United Kingdom |
| Ipswich Hospital | Ipswich | United Kingdom |
| Leeds General Infirmary/ St James' University Hospital | Leeds | LS1 3EX | United Kingdom |
| University Hospitals of Leicester NHS Trust | Leicester | LE3 9QP | United Kingdom |
| Lincoln County Hospital | Lincoln | United Kingdom |
| Royal Liverpool University Hospital | Liverpool | United Kingdom |
| Homerton University Hospital | London | E9 6SR | United Kingdom |
| Charing Cross Hospital | London | United Kingdom |
| Northwick Park Hospital | London | United Kingdom |
| St Bartholomew's Hospital | London | United Kingdom |
| Luton and Dunstable Hospital | Luton | United Kingdom |
| Macclesfield District General Hospital | Macclesfield | United Kingdom |
| Maidstone Hospital | Maidstone | United Kingdom |
| Hillingdon Hospital | Middlesex | United Kingdom |
| Milton Keynes General Hospital | Milton Keynes | United Kingdom |
| Norfolk and Norwich University Hospital | Norwich | United Kingdom |
| Nottingham City Hospital | Nottingham | United Kingdom |
| Derriford Hospital | Plymouth | United Kingdom |
| Dorset County Hospital | Poole | United Kingdom |
| Queen's Hospital, | Romford | United Kingdom |
| Salford Royal Hospital | Salford | M6 8HD | United Kingdom |
| Salisbury District Hospital | Salisbury | United Kingdom |
| Weston Park Hospital | Sheffield | United Kingdom |
| Southampton General Hospital | Southampton | United Kingdom |
| Staffordshire General Hospital | Stafford | ST16 3SA | United Kingdom |
| Stepping Hill Hospital | Stockport | United Kingdom |
| University Hospital of North Tees | Stockton-on-Tees | TS19 8PE | United Kingdom |
| Musgrove Park Hospital | Taunton | United Kingdom |
| St George's Hospital, | Tooting | United Kingdom |
| Torbay District General Hospital | Torquay | TQ2 7AA | United Kingdom |
| Royal Cornwall Hospital | Truro | TR1 3LJ | United Kingdom |
| Mid Yorkshire Hospitals | Wakefield | United Kingdom |
| Warwick Hospital | Warwick | CV34 5BW | United Kingdom |
| Royal Albert Edward Infirmary | Wigan | United Kingdom |
| Worthing Hospital | Worthing | United Kingdom |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D047072 | Aromatase Inhibitors |
| D000077384 | Anastrozole |
| D000077289 | Letrozole |
| ID | Term |
|---|---|
| D065088 | Steroid Synthesis Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D004965 | Estrogen Antagonists |
| D006727 | Hormone Antagonists |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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