This is a randomized double-blind placebo-controlled phase III trial of aspirin (300 mg daily) in early stage node-positive HER2 negative breast cancer patients. Patients will be randomized 1:1 within stratum defined by: Hormone Receptor status (HR positive vs HR negative), body mass index (<30 vs ≥ 30 kg/m2) and stage (Stage II vs III).
The primary objective of this trial is to compare the effect of aspirin versus placebo upon invasive disease free survival (iDFS).
Primary objective To compare the effect of aspirin (300 mg daily) versus placebo upon invasive disease free survival (iDFS) in early stage node-positive HER2 negative breast cancer patients.
1. To compare the effect of aspirin versus placebo in early stage node-positive HER2 negative breast cancer patients upon:
1. Distant disease-free survival
2. Overall survival
3. Cardiovascular disease (see Section11.3)
2. To compare the toxicity of aspirin versus placebo in early stage node-positive HER2 negative breast cancer patients.
3. To assess adherence to aspirin and placebo among early stage node-positive HER2 negative breast cancer patients.
4. To bank tumor and germline deoxyribonucleic acid (DNA), plasma and urine collected at baseline and sequential plasma and urine collected 2 years later for future measurement of inflammatory markers.
5. To determine if there are subgroups of participants characterized by lifestyle factors associates with greater inflammation for whom there is greater benefit of aspirin versus placebo upon iDFS.
Patients are followed up to 10 years after study enrollment.
1. Documentation of Disease - Histologic Documentation: Histologic documentation of women or men with node positive, HER2 negative, anatomic stage II or III breast carcinoma within one year of diagnosis and free of recurrence. If neoadjuvant therapy was received, either initial clinical stage (determined by physical and or radiologic examination) or post-operative pathologic stage can be used for eligibility purposes, with the higher stage determining eligibility. Histologic documentation of node positivity is required.
2. Disease status - Any ER/PgR status allowed.
3. Prior Treatment - Prior adjuvant treatment with chemotherapy and/or endocrine therapy, as determined the treating physician, is allowed. The last dose of chemotherapy or radiation therapy must be at least 60 days prior to study registration. Concurrent hormonal therapy will be allowed.
4. Regular NSAID/aspirin use (defined as ≥ 5 days per week) is allowed if aspirin and/or NSAIDs are stopped for one year prior to study entry and throughout the study period. Participants will be encouraged to use acetaminophen for minor pain and fever.
5. Patients must be enrolled within 1 year after diagnosis.
6. Age > 18 and < 70 years of age.
7. ECOG performance status 0-2.
8. Patients with a prior history of gastric/duodenal ulcers documented on endoscopy can be enrolled as long as the ulcers did not cause bleeding requiring a blood transfusion/major intervention.
9. For patients who are Helicobacter pylori positive, a course of Helicobacter pylori eradication treatment must have been completed.
10. No history of GI bleeding requiring a blood transfusion, endoscopic or operative intervention.
11. No history of any prior stroke (hemorrhagic or ischemic).
12. No concurrent anticoagulation with warfarin or heparin or clopidogrel or oral direct thrombin inhibitors.
13. No history of atrial fibrillation or myocardial infarction.
14. No history of grade 4 hypertension, defined as hypertension resulting in life-threatening consequences (e.g., malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis).
15. No chronic (duration >30 days) daily use of oral steroids.
16. No known allergy to aspirin.
17. No prior malignancy of any type within the past 5 years other than breast cancer, basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
18. Concurrent enrollment on a non-chemotherapy treatment trial will be allowed, as long as that trial allows concurrent daily aspirin use.
19. Required Initial Laboratory Values Platelet count ≥ 100,000/mm3
|Maximum Eligible Age:||69 Years|
|Minimum Eligible Age:||18 Years|