Letrozole in Preventing Cancer in Postmenopausal Women Who Have Received 4-6 Years of Hormone Therapy for Hormone Receptor-Positive, Lymph Node-Positive, Early-Stage Breast Cancer

OBJECTIVES:

Primary

• Compare the disease-free survival (DFS) of postmenopausal women treated with continuous letrozole for 5 years vs intermittent letrozole over a 5-year period.

Secondary

• Compare overall survival of patients treated with these two regimens.
• Compare distant DFS of these patients.
• Compare breast cancer-free interval of these patients.
• Compare sites of first DFS failure in these patients.
• Compare second (nonbreast) malignancies in these patients.
• Compare deaths without prior cancer events in these patients.
• Compare adverse events resulting from these two regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to treatment center and type of prior endocrine therapy (selective estrogen receptor modulators [SERMs] alone vs aromatase inhibitors [AIs] alone vs both SERMs and AIs each for at least 1 month). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral letrozole daily for 5 years.
• Arm II: Patients receive oral letrozole daily for the first 9 months of years 1 through 4, followed by 12 months in year 5.

After completion of study therapy, patients are followed annually.

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of prior operable, noninflammatory breast cancer meeting the following criteria:

• Steroid hormone receptor-positive tumors (estrogen receptor and/or progesterone receptor), determined by immunohistochemistry, after primary surgery and before commencement of prior endocrine therapy
• Prior local treatment including surgery with or without radiotherapy for primary breast cancer with no known clinical residual loco-regional disease
• Following primary surgery, eligible patients must have had evidence of lymph node involvement either in the axillary or internal mammary nodes, but not supraclavicular nodes
• Clinically disease-free
• Must have completed 4-6 years of prior adjuvant selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or a sequential combination of both

• When calculating 4-6 years, neoadjuvant endocrine therapy should not be included
• No evidence of recurrent disease or distant metastatic disease
• No prior bilateral breast cancer

PATIENT CHARACTERISTICS:

• Female
• Must be postmenopausal by any of the following criteria:

• Patients of any age who have had a bilateral oophorectomy (including radiation castration AND amenorrheic for > 3 months)
• Patients 56 years old or older with any evidence of ovarian function must have biochemical evidence of definite postmenopausal status (defined as estradiol, luteinizing hormone [LH], and follicle-stimulating hormone [FSH] in the postmenopausal range)
• Patients 55 years old or younger must have biochemical evidence of definite postmenopausal status (defined as estradiol, LH, and FSH in the postmenopausal range)

• Patients who have received prior luteinizing-hormone releasing-hormone (LHRH) analogues within the last year are eligible if they have definite evidence of postmenopausal status as defined above
• Clinically adequate hepatic function
• No bone fracture due to osteoporosis at any time during the 4-6 years of prior therapy
• No prior or current malignancy except adequately treated basal cell or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, or contra- or ipsilateral in situ breast carcinoma
• No other nonmalignant systemic diseases (cardiovascular, renal, lung, etc.) that would prevent prolonged follow-up
• No psychiatric, addictive, or any other disorder that compromises compliance with protocol requirements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 12 months since prior and no other concurrent endocrine SERM/AI therapy
• Any type of prior adjuvant therapy allowed including, but not limited to, any of the following:

• Neoadjuvant chemotherapy
• Neoadjuvant endocrine therapy
• Adjuvant chemotherapy
• Trastuzumab (Herceptin®)
• Ovarian ablation
• Gonadotropin releasing hormone analogues
• Lapatinib ditosylate
• No concurrent hormone-replacement therapy, bisphosphonates (except for treatment of bone loss), or any other investigational agent