Exemestane in Treating Postmenopausal Women With Resected Stage I, Stage II, or Stage IIIA Breast Cancer Who Have Completed 5 Years of Tamoxifen
Exemestane in Treating Postmenopausal Women With Resected Stage I, Stage II, or Stage IIIA Breast Cancer Who Have Completed 5 Years of Tamoxifen
RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using
 exemestane may fight breast cancer by reducing the production of estrogen by the tumor cells.
 It is not yet known whether exemestane is effective in preventing the recurrence of breast
 cancer.

 PURPOSE: Randomized phase III trial to study the effectiveness of exemestane in preventing
 cancer recurrence in postmenopausal women who have resected stage I, stage II, or stage IIIA
 breast cancer and have completed 5 years of tamoxifen.
OBJECTIVES:

 -  Determine whether the administration of 5 years of exemestane after 5 years of tamoxifen
 therapy is more effective than 5 years of prior tamoxifen therapy alone in prolonging
 disease-free survival, overall survival, and time to treatment failure in postmenopausal
 women with resected stage I, II, or IIIA breast cancer.

 -  Determine the effect of tamoxifen withdrawal on bone, in terms of height, fractures, and
 total alkaline phosphatase in these patients and on bone mineral density and bone
 biochemical markers in a subset of patients.

 -  Determine the effect of exemestane on bone loss after tamoxifen withdrawal in these
 patients.

 -  Evaluate the quality of life of a subset of these patients.

 OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

 -  Arm I: Patients receive oral exemestane daily for 5 years.

 -  Arm II (closed as of 10/15/03): Patients receive an oral placebo daily for 5 years.

 Quality of life is assessed at baseline and then every 6 months for 5.5 years.

 Patients are followed every 6 months for 6 years and then annually thereafter.

 PROJECTED ACCRUAL: A total of 3,000 patients will be accrued for this study within 3 years
 and 4 months.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed invasive adenocarcinoma of the breast at time of original
 diagnosis

 -  Tumor confined to the breast and ipsilateral axilla on clinical exam (T1-3, N0-1,
 M0) (stage I-IIIA)

 -  No ipsilateral lymph nodes clinically fixed to one another or to other structures
 (N2 disease) at time of original diagnosis

 -  Prior surgical resection, including 1 of the following:

 -  Total mastectomy and axillary dissection (modified radical mastectomy) OR

 -  Lumpectomy and axillary dissection

 -  Prior post-lumpectomy breast radiotherapy required

 -  Prior sentinel node biopsy allowed with the exception of the following:

 -  If any sentinel node is histologically positive by hematoxylin and eosin (H
 & E) OR histologically suspicious on H & E and confirmed positive by
 immunohistochemistry then the patient must have a complete axillary
 dissection

 -  Previously resected margins must be clear of invasive tumor and ductal carcinoma
 in situ

 -  Currently disease free

 -  Previously treated with tamoxifen for 57-66 months

 -  Completed tamoxifen within the past 180 days

 -  No bilateral malignancy or mass in the opposite breast suspicious for malignancy
 unless biopsy proven negative

 -  No local, regional, or distant recurrence of disease or second primary breast
 malignancy (including contralateral breast cancer)

 -  No advanced disease at time of original diagnosis (e.g., ulceration, erythema,
 infiltration of the skin or underlying chest wall [complete fixation], peau d'orange,
 or skin edema of any magnitude)

 -  Tethering or dimpling of the skin or nipple inversion allowed

 -  Current skeletal pain allowed if a bone scan and/or radiologic exam is negative for
 metastatic disease

 -  Hormone receptor status:

 -  Primary tumor estrogen receptor (ER) positive AND/OR

 -  Progesterone receptor positive

 -  Borderline ER positive tumors allowed if previously treated with tamoxifen

 PATIENT CHARACTERISTICS:

 Age:

 -  Postmenopausal

 Sex:

 -  Female

 Menopausal status:

 -  Postmenopausal, defined as 1 of the following:

 -  Prior bilateral oophorectomy

 -  Absence of spontaneous menstrual cycle for more than 1 year

 -  Follicle-stimulating hormone within the postmenopausal range if under 55 and had
 a prior hysterectomy without a bilateral oophorectomy

 Performance status:

 -  Not specified

 Life expectancy:

 -  At least 10 years

 Hematopoietic:

 -  Absolute granulocyte count at least 1,500/mm^3

 -  Platelet count at least 100,000/mm^3

 -  Hemoglobin normal

 Hepatic:

 -  Bilirubin less than 2 times upper limit of normal (ULN)

 -  SGOT or SGPT no greater than 2.5 times ULN

 -  Alkaline phosphatase less than 2 times ULN

 -  No systemic hepatic disease that would preclude study participation

 Renal:

 -  Creatinine no greater than 1.5 times ULN

 -  No systemic renal disease that would preclude study participation

 Cardiovascular:

 -  No systemic cardiovascular disease that would preclude study participation

 Other:

 -  No other malignancy within the past 5 years except effectively treated squamous cell
 or basal cell skin cancer, surgically treated carcinoma in situ of the cervix, or
 surgically treated lobular carcinoma in situ of the ipsilateral or contralateral
 breast

 -  No nonmalignant systemic disease that would preclude study participation

 -  No psychiatric or addictive disorder that would preclude informed consent

 -  Not pregnant

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  Not specified

 Chemotherapy:

 -  Prior adjuvant chemotherapy allowed if administered concurrently with or prior to
 tamoxifen

 Endocrine therapy:

 -  See Disease Characteristics

 -  No concurrent estrogen, progesterone, clomiphene, testosterone, gonadotropin-releasing
 hormone, oral contraceptives, selective estrogen-receptor modulators, or
 dehydroepiandrosterone (DHEA)

 -  Estring or estrogen vaginal cream at 0.3 mg or 1/8 of an applicator applied
 vaginally 3 times a week allowed

 -  No other concurrent systemic hormonal therapy (e.g., tamoxifen or raloxifene)

 Radiotherapy:

 -  See Disease Characteristics

 -  Prior post-mastectomy loco-regional radiotherapy or post-lumpectomy regional
 radiotherapy allowed

 Surgery:

 -  See Disease Characteristics

 Other:

 -  Prior participation in other adjuvant NSABP study allowed if study was reported in
 peer-review publication or tamoxifen was not a study drug

 -  Concurrent bisphosphonates or calcitonin for prevention or treatment of osteoporosis
 allowed

 -  Concurrent statins (simvastatin, pravastatin, fluvastatin, atorvastatin, or
 lovastatin) or other drugs to control lipid levels allowed