A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer

Novartis

Status and phase: Completed; Phase 3

Conditions: Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women

Treatments: Drug: Tamoxifen; Drug: Letrozole

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00171704

CFEM345D2407

Details and patient eligibility

About

Estrogen is known to be a regulator of bone and lipid metabolism. Letrozole is a potent inhibitor of estrogen synthesis.

This study evaluated the effects of letrozole and tamoxifen on bone and lipid metabolism in postmenopausal women with resected, receptor positive early breast cancer.

Enrollment: 263 patients

Sex: Female

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Female
• Post-menopausal hormone status defined as:
• Patients with menostasis (amenorrhea) > 12 months or history of oophorectomy.
• Patients ≥ 55 years with history of hysterectomy or having continued/renewed menstruation on cyclic hormone treatment.
• Patients of 50-54 years: Menopausal status was determined on the basis of follicle-stimulating hormone (FSH)/luteinizing hormone (LH) values.
• Histologically confirmed resected breast cancer and eligible for adjuvant endocrine therapy. As a minimum, patients had to have receptor-positive tumors, which were defined either as estrogen receptor (ER) and/or progesterone receptor (PgR) ≥ 10 fmol/mg cytosol protein; or ≥ 10% of the tumor cells positive by immunocytochemical evaluation.
• Adequate bone marrow function (white blood cell count [WBC] > 3.0 x 109 /L, platelets ≥ 100.0 x 109 /L, and hemoglobin > 10 g/dL).
• Documented evidence of adequate renal function (creatinine < 180 µmol/L) and hepatic function (bilirubin < 30 µmol/L, alanine aminotransferase (ALT) < 1.5 x upper normal limit of the laboratory).
• Life expectancy of at least 24 months at the time of enrollment.
• Written voluntary informed consent prior to initiation of any study procedure.
• Willingness to undergo all scheduled tests and examinations for evaluation of bone density and bone metabolism, and lipid profiles in addition to the standard assessments for monitoring their breast cancer status.

Exclusion Criteria

• Patients with distant metastases as defined by the criteria of the Danish Breast Cancer Co-operative Group (DBCCOG).
• Pre-existing bone disease (e.g. osteomalacia, osteogenesis imperfecta, Paget's disease).
• Patients receiving bisphosphonates for more than 3 months before randomization.
• Chronic treatment with drugs known to interfere with bone metabolism, e.g.
• Anti-convulsants within the past year.
• Corticosteroids at doses greater than the equivalent of 5 mg/day prednisone for more than two weeks in the past 6 months (prior to randomization).
• Any previous treatment with sodium fluoride at daily doses ≥ 5 mg/day for a period exceeding 1 month.
• Anabolic steroids in the past 12 months.
• Long term use of coumarin derivatives and heparin at the time of randomization.
• Metabolic diseases known to interfere with bone metabolism (e.g., Hyperparathyroidism, hypoparathyroidism, uncontrolled thyroid disease, Cushing's disease, vitamin D deficiency, malabsorption syndrome, etc.).
• Treatment with lipid-lowering agents within the 3 months prior to randomization (this exclusion criterion did not apply to patients randomized in the United Kingdom).
• Patients receiving other anti-cancer treatment.
• Previous neoadjuvant / adjuvant chemotherapy and /or previous adjuvant endocrine therapy (e.g., anti-estrogens, AIs).
• History of previous or concomitant malignancy within the past 5 years other than adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who had a previous other malignancy must have been disease free for five years. Patients with endometrial cancer and/or invasive breast cancer at any time in their medical history were excluded. Patients with invasive bilateral breast cancer were excluded. Patients with vaginal discharge/ vaginal bleeding with evidence of malignancy were excluded.
• Any other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

263 participants in 2 patient groups

Letrozole

Experimental group

Description:

2.5 mg once daily (q.d.)orally for 5 years

Treatment:

Drug: Letrozole

Tam-Let

Experimental group

Description:

20 mg Tamoxifen once daily (q.d.) orally for 2 years followed by Letrozole 2.5 mg q.d. orally for 3 years.

Treatment:

Drug: Letrozole

Drug: Tamoxifen