A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer
Condition: Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women
MeSH terms: Breast Neoplasms
Intervention: Letrozole; Tamoxifen
Intervention description: 2.5 mg tablets and supplied in bottles with 6-monthly supplies.; 20 mg tablets in bottles as 6-monthly supplies (supplied to Novartis as Tamofen from Schering Oy, Subsidiary of Schering AG, Pansiontie 47, FIN-2010 Turku, Finland)
Intervention MeSH terms: Tamoxifen; Letrozole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 263.0
Sex: Female
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Breast Cancer; Letrozole; Bone Mineral Density; Bone Markers; Serum lipid; Postmenopausal

Summary:

      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.
    

Eligibility 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.