Exemestane Compared With Anastrozole, With or Without Celecoxib, in Treating Postmenopausal Women After Surgery for Primary Breast Cancer

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using exemestane or anastrozole may fight breast cancer by reducing the production of estrogen. It is not yet known whether exemestane is more effective than anastrozole, with or without celecoxib, in preventing the recurrence of breast cancer.

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using exemestane or anastrozole may fight breast cancer by reducing the production of estrogen. It is not yet known whether exemestane is more effective than anastrozole, with or without celecoxib, in preventing the recurrence of breast cancer. PURPOSE: Randomizedphase III trial to compare the effectiveness of exemestane with that of anastrozole, with or without celecoxib, in preventing cancer recurrence in postmenopausal women who have undergone surgery for primary breast cancer. Condition:- Breast CancerStudy Type: InterventionalStudy Design: Treatment Official Title: Phase III Randomized Adjuvant Study of Exemestane Versus Anastrozole With or Without Celecoxib in Postmenopausal Women With Receptor-Positive Primary Breast Cancer Further Study Details: OBJECTIVES:Compare the event-free survival of postmenopausal women with receptor-positive primary breast cancer when treated with exemestane vs anastrozole as adjuvant therapy with or without celecoxib. Compare the overall survival of patients treated with these regimens. Compare the time to distant recurrence in patients treated with these regimens. Compare the incidence of new primary contralateral breast cancer in patients treated with these regimens. Compare the incidence of all clinical fractures, specifically hip and vertebral fractures, in patients treated with these regimens. Compare cardiovascular morbidity and mortality (i.e., significant coronary heart disease, which includes myocardial infarctions and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes, and all vascular deaths) in patients treated with these regimens. Compare the toxic effects of these regimens in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to lymph node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), and current low-dose (no more than 81 mg/day) prophylactic aspirin use (yes vs no). Patients are randomized to 1 of 4 treatment arms. Arm I: Patients receive oral exemestane once daily for 5 years and oral celecoxib twice daily for 3 years. Arm II: Patients receive exemestane as in arm I and oral placebo twice daily for 3 years. Arm III: Patients receive oral anastrozole once daily for 5 years and celecoxib as in arm I. Arm IV: Patients receive anastrozole as in arm III and oral placebo twice daily for 3 years. In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed annually.PROJECTED ACCRUAL: A total of 6,830 patients (approximately 1,707 per treatment arm) will be accrued for this study within 4 years. Eligibility Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both Criteria DISEASE CHARACTERISTICS:Histologically confirmed invasive breast cancer pT1-3; pNX, pN0-2 or pN3*; M0 NOTE: *Only when the sole basis for this classification is the presence of 10 or more involved axillary lymph nodes Completely resected disease Primary surgery performed at least 3 weeks but no more than 3 months before study entry (if no chemotherapy or radiotherapy was given) No metastases confirmed by 1 of the following methods: Bone scan** (required only if alkaline phosphatase is at least 2 times normal and/or there are symptoms of metastatic disease) Abdominal ultrasound or CT scan (required only if AST/ALT or alkaline phosphatase is at least 2 times normal, unless the elevation is in the bone fraction) Chest x-ray NOTE: **Confirmatory x-ray, CT scan, or MRI required if the bone scan results are questionable No locally recurrent disease Synchronous bilateral breast cancer allowed No metachronous breast cancer Hormone receptor status: Estrogen receptor and/or progesterone receptor positive by immunohistochemistry At least 1 tumor must be receptor positive in patients with bilateral breast cancer PATIENT CHARACTERISTICS: AgePostmenopausal SexFemale Menopausal statusPostmenopausal defined as 1 of the following: Over 55 years of age with no spontaneous menses for at least 1 year Age 55 and under with no menses (spontaneous or secondary to hysterectomy) within the past year AND a follicle-stimulating hormone level in the postmenopausal range (by institutional standards or greater than 34.4 IU/L if institutional range is not available) Bilateral oophorectomy Performance statusECOG 0-2 Life expectancyAt least 5 years HematopoieticWBC at least 3,000/mm OR Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 HepaticSee Disease Characteristics AST and/or ALT less than 2 times upper limit of normal (ULN)* Alkaline phosphatase less than 2 times ULN* NOTE: *Unless imaging examinations have ruled out metastatic disease RenalCreatinine less than 1.5 times ULN OtherAdequate unassisted oral intake No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix No known active or incompletely treated peptic ulcer disease No known allergy to sulfonamides No prior asthma, urticaria, or allergic-type reaction to aspirin or other NSAIDs No other concurrent medical or psychiatric condition that would preclude study participation and/or interfere with results PRIOR CONCURRENT THERAPY: Biologic therapyNot specified ChemotherapySee Disease Characteristics At least 3 weeks but no more than 3 months since prior chemotherapy Prior adjuvant chemotherapy allowed Endocrine therapyNo prior aromatase inhibitor No prior tamoxifen or other selective estrogen receptor modulators except raloxifene At least 3 weeks since prior raloxifene No concurrent estrogens, progesterones, androgens, or selective estrogen-receptor modulators Concurrent intermittent vaginal estrogens allowed if other local measures for intractable vaginal atrophy are insufficient No other concurrent endocrine therapy No other concurrent hormonal therapy No concurrent steroids RadiotherapySee Disease Characteristics Prior adjuvant radiotherapy allowed Concurrent radiotherapy allowed SurgerySee Disease Characteristics OtherNo prior treatment on another trial for breast cancer unless permission has been obtained from the sponsors of the original study At least 3 weeks since prior over-the-counter products or supplements considered to have an estrogenic effect, including any of the following: Ginseng Ginkgo biloba Black cohosh Dong quai Fortified soy supplements (e.g., phytoestrogen preparations) No concurrent over-the-counter products or supplements considered to have an estrogenic effect No concurrent chronic nonsteroidal anti-inflammatory drugs (NSAIDs) No concurrent cyclooxygenase (COX)-2 inhibitors (e.g., rofecoxib) No concurrent medication that would effect study endpoints Concurrent low-dose prophylactic aspirin (81 mg/day or less) allowed Concurrent bisphosphonates allowed for prevention or treatment of osteoporosis [1] National Cancer Institute of Canada[2] Central Cancer Treatment Group[3] Cancer and Leukemia Group B[4] Eastern Cooperative Oncology Group[5] Southwest Oncology Group