Letrozole in Treating Breast Cancer in Postmenopausal Women With Stage I, Stage II, or Stage III Breast Cancer Previously Treated With Tamoxifen

• Overall survival [ Designated as safety issue: No ]
• Safety [ Designated as safety issue: Yes ]

RATIONALE: Estrogen can cause the growth of breast cancer cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known which regimen of letrozole is most effective in treating breast cancer in postmenopausal women who have received tamoxifen.

PURPOSE: This randomized phase III trial is comparing different regimens of letrozole to see how well they work in treating postmenopausal women with stage I, stage II, or stage III breast cancer previously treated with tamoxifen.

OBJECTIVES:

Primary

• To compare the disease-free survival of previously treated, post-menopausal women with early-stage breast cancer treated with standard- (2-3 years of tamoxifen followed by 2-3 years of letrozole) versus long-treatment (2-3 years of tamoxifen followed by 5 years of letrozole) adjuvant letrozole.

Secondary

• To compare the overall survival of these patients.
• To compare the safety of these patients.

OUTLINE: Patients are randomized to 1 or 2 treatment arms.

• Arm I (standard treatment): Patients previously treated with tamoxifen for 2 years receive letrozole for an additional 3 years; patients previously treated with tamoxifen for 3 years receive letrozole for an additional 2 years; and patients previously treated with tamoxifen for 2-3 years receive letrozole , so the total duration of the endocrine treatment (i.e., tamoxifen followed by letrozole) is 5 years.
• Arm II (long treatment): Patients receive letrozole for an additional 5 years regardless of the duration of the previous tamoxifen treatment.

• Drug: letrozole
• Procedure: adjuvant therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer at first diagnosis

  • Stage I, II, or III disease
  • Documented (microscopic) infiltration of the skin (pT4) allowed
• Nx, pNo, pN1, pN2, PN3 axillary nodal status allowed

• Received adjuvant tamoxifen for at least 2 years but no more than 3 years and 3 months

  • Patients treated with adjuvant chemotherapy must have begun receiving tamoxifen within 3 months after the completion of chemotherapy
• Definitive surgical treatment must be either mastectomy or breast-conserving surgery with axillary lymph node dissection OR sentinel node biopsy for operable breast cancer
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• ECOG or WHO performance status 0-1

• Post-menopausal status meeting 1 of the following criteria:

  • Age > 55 years with cessation of menses
  • Age < 55 years but no spontaneous menses for at least 1 year
  • Age < 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy), AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved
  • Underwent a bilateral oophorectomy
• Must be accessible for treatment and follow-up

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior aromatase inhibitors allowed
• Concurrent bisphosphonates allowed