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A Phase III Study to Evaluate Letrozole as Adjuvant Endocrine Therapy for Postmenopausal Women With Receptor (ER and/or PgR) Positive Tumors

Phase 3
30 Years
Open (Enrolling)
Breast Cancer

Thank you

Trial Information

A Phase III Study to Evaluate Letrozole as Adjuvant Endocrine Therapy for Postmenopausal Women With Receptor (ER and/or PgR) Positive Tumors


- Compare adjuvant letrozole vs tamoxifen administered for 5 years in postmenopausal
women with operable, hormone receptor-positive breast cancer.

- Compare these treatment regimens given sequentially vs continuously in this patient

- Compare these treatment regimens in terms of overall survival, disease-free and
systemic-free survival, safety, and tolerability in this patient population.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified
according to adjuvant chemotherapy (prior therapy vs no prior or concurrent therapy vs
concurrent therapy), prior surgery (modified radical mastectomy vs a lesser surgical
procedure), and participating center. Patients are randomized to one of four treatment arms.

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

- Arm II: Patients receive adjuvant oral letrozole daily for 5 years.

- Arm III: Patients receive adjuvant oral tamoxifen daily for 2 years followed by
adjuvant oral letrozole daily for 3 years.

- Arm IV: Patients receive adjuvant oral letrozole daily for 2 years followed by adjuvant
oral tamoxifen daily for 3 years.

Patients may receive concurrent radiotherapy. Some patients receive concurrent adjuvant
chemotherapy beginning within 8 weeks after surgery and continuing for no more than 6

Patients are followed annually.

PROJECTED ACCRUAL: A total of 5,180 patients (1,295 per treatment arm) will be accrued for
this study within 6 years.

Inclusion Criteria


- Histologically confirmed resectable adenocarcinoma of the breast

- pT1, pT2, pT3, or minimal dermal involvement on pathology only

- pN0, pN1, pN2, or M0

- Negative nodal status

- At least 8 nodes are negative

- Unknown nodal status

- Less than 8 nodes examined and no pathological finding

- Positive nodal status

- Any positive finding independent of the number of nodes examined

- Negative sentinel node or no prior nodal dissection allowed if all other
criteria met

- Must have had total mastectomy, lumpectomy, or quadrantectomy

- Should have prior chest wall radiotherapy after segmental mastectomy or
histopathologic T4 dermal involvement

- Stage I, II, or IIIa allowed if the tumor is completely removed macroscopically and
margins of the resected tumor are microscopically free of tumor

- Must undergo chest wall radiotherapy or second resection if microscopic disease at
the mastectomy margins

- No bilateral disease except in situ disease, either ductal or lobular of the
contralateral breast

- Postmenopausal

- Regardless of prior hormonal replacement therapy (HRT) or hysterectomy:

- Bilateral oophorectomy and any age

- Radiologic castration and amenorrheic for at least 3 months and any age

- Not postmenopausal at the start of adjuvant chemotherapy AND and completed
at least 6 courses of prior cyclophosphamide, methotrexate, and
fluorouracil (CMF) or at least 4 courses of prior
anthracycline-cyclophosphamide continuation therapy and at least age 45
with follicle stimulating hormone (FSH), luteinizing hormone (LH), and
estradiol (E2) postmenopausal levels

- No prior HRT:

- Prior hysterectomy and less than age 55 with FSH/LH/E2 postmenopausal

- Prior hysterectomy and at least age 55

- No prior HRT or hysterectomy:

- Amenorrhea more than 1 year and less than age 50

- Amenorrhea more than 6 months and at least age 50

- Prior HRT regardless of hysterectomy:

- At least 1 month since prior HRT and less than age 55 with FSH/LH/E2
postmenopausal levels

- At least 1 month since prior HRT and at least age 55

- FSH/LH/E2 postmenopausal levels and uncategorized

- No distant metastases, including bone scans showing hot spots unconfirmed as benign
disease or skeletal pain of unknown cause

- At least 10% hormone receptor-positive tumor cells

- Hormone receptor status:

- Estrogen receptor positive AND/OR

- Progesterone receptor positive



- 30 and over


- Female

Menopausal status:

- Postmenopausal

Performance status:

- Not specified

Life expectancy:

- Not specified


- WBC greater than 3,000/mm^3

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

- Hemoglobin greater than 10 g/dL


- Bilirubin less than 3.0 mg/dL

- SGOT or SGPT less than 1.5 times upper limit of normal

- No hepatic disease that would preclude study


- Creatinine less than 1.8 mg/dL

- No renal disease that would preclude study


- No cardiovascular disease that would preclude study

- Prior deep vein thrombosis allowed if medically stable


- No lung embolism


- No other prior or concurrent malignancy within the past 5 years except adequately
treated basal or squamous cell skin cancer or carcinoma in situ of the cervix

- No prior noncompliance to medical regimens

- No other nonmalignant systemic diseases that would preclude follow-up

- HIV negative


Biologic therapy:

- Prior immunotherapy or biological response modifiers (e.g., interferon) allowed


- See Disease Characteristics

- Prior adjuvant or neoadjuvant chemotherapy allowed

- Concurrent adjuvant chemotherapy allowed

Endocrine therapy:

- See Disease Characteristics

- Prior neoadjuvant hormonal therapy allowed (e.g., antiestrogens, progestins, or
aromatase inhibitors) if no more than 4 months duration and no disease progression

- Prior corticosteroids allowed

- At least 4 weeks since prior HRT

- Prior adjuvant antiestrogen therapy allowed if less than 1 month duration and
immediately after surgery, radiotherapy, and/or chemotherapy

- Prior antiestrogens for chemoprevention allowed if at least 18 months between
completion of chemoprevention and diagnosis

- No other concurrent antiestrogens or aromatase inhibitors

- No concurrent raloxifene

- No concurrent systemic HRT with or without progestins of more than 3 months duration


- See Disease Characteristics

- Concurrent radiotherapy allowed


- See Disease Characteristics


- At least 30 days since prior systemic investigational drugs

- At least 7 days since prior topical investigational drugs

- Concurrent bisphosphonates allowed

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Disease free survival.

Outcome Description:

Time from randomization to recurrence (including recurrence restricted to the breast after breast conserving treatment), metastasis, appearance of a second primary tumor, or death from any cause, whichever occurs first.

Outcome Time Frame:

Until patient's death (lifelong follow-up).

Safety Issue:


Principal Investigator

Beat Thurlimann, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Kantonsspital St. Gallen


Australia: Department of Health and Ageing Therapeutic Goods Administration

Study ID:




Start Date:

March 1998

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • breast cancer in situ
  • recurrent breast cancer
  • ductal breast carcinoma
  • lobular breast carcinoma in situ
  • Breast Neoplasms