Dataset 

Inclusion Criteria:

Inclusion Criteria:

•  Completely resected (greater or equal 1mm), histologically or cytologically proven unilateral breast cancer

•  Female greater or equal 18 years of age

•  If (neo) adjuvant chemotherapy received, patient must have received at least 4 cycles. Chemotherapy must be completed prior to study entry

•  Hormone Receptor negatives must have received prior chemotherapy

•  Study entry must be within any of the following timelines: 3 months of the end of definitive breast surgery OR between 3 weeks and 4 months after day 1 of the last cycle of adjuvant chemotherapy OR 6 weeks of the end of radiotherapy.

•  WHO performance status 0 or 1

•  Pre-treatment haematology and biochemistry values within acceptable local limits: Haemoglobin, white blood cell greater or equal to 3.0 x 109/l or absolute neutrophil count greater or equal to 1.51 x 109/l, Platelets greater or equal to 100 x 109/l, Serum bilirubin less than 1.5 x upper normal limit , Alkaline phosphatase less or equal to 1.5 x upper normal limit , Serum creatinine less than 1.5 x upper normal limit

•  Negative pregnancy test for patients with child-bearing potential

•  Normal baseline ECG and clinical cardiovascular assessment after completion of all (neo) adjuvant chemotherapy

•  No previous or current evidence for metastatic disease

•  Be accessible for and consent to long term follow-up

•  Written informed consent prior to commencement of specific protocol procedures must be obtained and documented according to the local regulatory requirements

Exclusion Criteria

•  Patients with node negative, T1, Grade 1 breast cancer

•  Unresectable, metastatic or bilateral breast cancer

•  Active or previous peptic ulceration or gastrointestinal bleeding in the last year

•  Active or previous history of inflammatory bowel disease

•  A past history of adverse reaction/hypersensitivity to NSAIDs, including celecoxib and salicylates, or sulphonamides

•  On current or planned chronic NSAIDs therapy (except low dose aspirin 100 mg four times per day or 325mg once daily).

•  Current or long-term use of oral corticosteroids

•  Known or suspected congestive heart failure (greater than New York Heart Association I) and/or coronary heart disease, previous history of myocardial infarction, uncontrolled arterial hypertension (ie BP greater than 160/90mmHg) under treatment with two anti-hypertensive drugs, rhythm abnormalities requiring permanent treatment.

•  Patients with diabetes controlled by diet and oral medication are eligible for the study however patients with insulin dependent diabetes are excluded

•  Past history of stroke/Transient ischaemic attack, symptomatic peripheral vascular disease or carotid disease

•  Previously entered into an adjuvant chemotherapy trial for which approval for entry into REACT has not been granted

•  ER receptor status unknown, Human epidermal growth factor receptor 2 or FISH positive, or Human epidermal growth factor receptor 2 status unknown

•  14. Hormone Receptor negative and not received (neo)adjuvant chemotherapy 15. Use of hormone replacement therapy within the last 6 weeks 16. Pregnant or lactating women or women of childbearing potential unwilling/unable to use non-hormonal contraception 17. No previous or concomitant malignancies except adequately treated squamous cell / basal cell carcinoma of the skin, in situ carcinoma of the cervix or ductal carcinoma in situ/lobular carcinoma in situ of the breast, unless there has been a disease-free interval of 10 years or more 18. Psychiatric or addictive disorders which could preclude obtaining informed consent 19. Clinical evidence of severe osteoporosis and/or history of osteoporotic fracture

Intervention

INTERVENTION 1:

•  Celecoxib

•  Patients in this arm will receive 400mg of celecoxib once daily. In addition, Hormone Receptor (+) patients will receive endocrine treatment according to local practice.

•  Celecoxib: Patients will receive 400mg of Celecoxib once daily for two years or until disease progression (if before the two years limit) or until development of unacceptable toxicities. In addition ER(+) patients will receive endocrine treatment according to local practice.

INTERVENTION 2:

•  Placebo

•  Patients in this arm will receive 2 tablets once daily. In addition Hormone Receptor (+) patients will receive endocrine treatment according to local practice.

•  Placebo: Two capsules once daily with food

Results

Outcome Measurement:

•  Disease Free Survival (DFS) Benefit of Two Years Adjuvant Therapy With the COX-2 Inhibitor Celecoxib Compared With Placebo in Primary Breast Cancer Patients.

•  From time of randomisation to the date of first event; with events contributing to the analysis defined as loco-regional and distant breast cancer recurrence, new primary breast cancer (ipsilateral or contralateral) and death without disease relapse (intercurrent death)

•  Time frame: Patients will be followed up to 10 years. DFS will be calculated from date of randomization until the date of first documented DFS event, this will be assessed at 2 and 5 years

Results 1:

•  Arm/Group Title: Celecoxib

•  Arm/Group Description: Patients in this arm will receive 400mg of celecoxib once daily. In addition, Hormone Receptor (+) patients will receive endocrine treatment according to local practice.

•  Celecoxib: Patients will receive 400mg of Celecoxib once daily for two years or until disease progression (if before the two years limit) or until development of unacceptable toxicities. In addition ER(+) patients will receive endocrine treatment according to local practice.

•  Overall Number of Participants Analyzed: 1763

•  Measure Type: Number

•  Unit of Measure: Percentage of participants  2 Year DFS rate: 91    (90 to 93)

•  5 Year DFS rate: 84    (82 to 86)

Results 2:

•  Arm/Group Title: Placebo

•  Arm/Group Description: Patients in this arm will receive 2 tablets once daily. In addition Hormone Receptor (+) patients will receive endocrine treatment according to local practice.

•  Placebo: Two capsules once daily with food

•  Overall Number of Participants Analyzed: 876

•  Measure Type: Number

•  Unit of Measure: Percentage of participants  2 Year DFS rate: 90    (87 to 92)

•  5 Year DFS rate: 83    (81 to 86)

Adverse events

Adverse Events 1:

•  Total: 148/1755 (8.43%)

•  Anaemia  1/1755 (0.06%)

•  Neutropenia  0/1755 (0.00%)

•  Thrombocytopenia  0/1755 (0.00%)

•  Thrombocytopenic purpura 1/1755 (0.06%)

•  Acute cardiac event  1/1755 (0.06%)

•  Aortic valve incompetence  1/1755 (0.06%)

•  Arrhythmia  1/1755 (0.06%)

•  Atrial fibrillation  1/1755 (0.06%)

•  Cardiac failure  0/1755 (0.00%)

•  Cardiac tamponade  0/1755 (0.00%)

Adverse Events 2:

•  Total: 64/868 (7.37%)

•  Anaemia 2/868 (0.23%)

•  Neutropenia 2/868 (0.23%)

•  Thrombocytopenia  1/868 (0.12%)

•  Thrombocytopenic purpura  0/868 (0.00%)

•  Acute cardiac event  0/868 (0.00%)

•  Aortic valve incompetence  0/868 (0.00%)

•  Arrhythmia  1/868 (0.12%)

•  Atrial fibrillation  0/868 (0.00%)

•  Cardiac failure  1/868 (0.12%)

•  Cardiac tamponade  1/868 (0.12%)