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Tamoxifen

Letrozole

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Estrogens

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Hormone Antagonists

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Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

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

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

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)

Novartis

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.

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

Lumbar spine (L2-L4) BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. The primary scanning site was the lumbar spine (L2 to L4) and the secondary scanning site was the total hip. All DXA scans were evaluated by a central reader.

Lumbar spine (L2-L4)BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. The primary scanning site was the lumbar spine (L2 to L4) and the secondary scanning site was the total hip. All DXA scans were evaluated by a central reader.

Total hip BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. All DXA scans were evaluated by a central reader.

Bone turnover markers (fasting serum procollagen-I extension peptide \[P1NP\], C-telopeptide \[CTX\], skeletal bone-specific alkaline phosphatase \[BSAP, N-telopeptide \[NTX\]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. The analysis of bone markers was based on analysis of variance of the regression slopes calculated for each individual patient and each bone marker over time. In the following summary, only the median treatment group percent change from baseline (and range) at 5 years is presented for each bone marker.

Serum lipid profile (fasting serum cholesterol \[total, HDL and calculated LDL\], triglycerides, and lipoprotein \[a\]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. The analysis of serum lipids was on the treatment group median percent change from baseline (and range) at 5 years.

Serum lipid profile (fasting serum cholesterol \[total, HDL and calculated LDL\], triglycerides, and lipoprotein \[a\]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. Numbers are not additive, as patients could be included in multiple rows.

Disease-free survival was defined as the interval between randomization and earliest confirmed event of loco-regional recurrence, distant metastases, invasive contralateral breast cancer, or death from any cause.

Overall survival was measured from date of randomization to date of death.

Danish Breast Cancer Cooperative Group

University of Sheffield

Novartis Pharmaceuticals

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

Tam-Let

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

Total

Age, Continuous

Sex: Female, Male

The study was designed to investigate the effects of letrozole compared with tamoxifen for 2 years on BMD spine (L2-L4). The study was too small to investigate the comparative efficacy of treatments on disease-free survival or on overall survival.

The safety population consisted of only patients who took randomized therapy for at least one day. The number of patients in each treatment arm who had completed 2 years of the study and had centrally assessed measurements of lumbar spine or total hip BMD.

Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine (L2-l4)

The safety population consisted of only patients who took randomized therapy for at least one day. The analysis at 5 years included all patients enrolled and who had centrally assessed measurements of lumbar spine and/or total hip BMD.

Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine

The safety population consisted of only patients who took randomized therapy for at least one day. The analysis of BMD at 5 years included all patients enrolled with centrally assessed measurements of total hip BMD.

Percent Change From Baseline of Bone Mineral Density (BMD) of Total Hip

Procollagen-I (PINP) (n=86, 78)

Bone Specific alkaline Phosphatase (n=87,78)

C-telopeptide (CTX) (n=88, 78)

N-telopeptide (NTX) (n=-88, 77)

The safety population consisted of only patients who took randomized therapy for at least one day. During different time points, participants with observations at that time point were included in the analysis. The analysis of bone markers over time consisted of patients with measurements of specific markers at each time point.

Median Percent Change From Baseline of Serum Markers of Bone Turnover

Total Cholesterol (n=91, 82)

LDL Cholesterol (n=91, 82)

HDL Cholesterol (n=91, 82)

The safety population consisted of only patients who took randomized therapy for at least one day. During different time points, participants with observations at that time point were included in the analysis.

Percentage Change From Baseline in Serum Lipids at 5 Years

Patients with one or more change

≥8 mmol/L total (T) cholesterol

≥7 mmol/L T.choles. & ≥1 risk for cardiac disease

≥6 mmol/L T. choles. & ≥2 risk for cardiac disease

The safety population consisted of only patients who took randomized therapy for at least one day. The number of patients with pre-defined clinically relevant changes in serum lipids over the course of 5 years in each treatment arm is presented.

Number of Participants With Clinically Relevant Changes From Baseline in Cholesterol

Analysis of disease-free survival was based on the ITT principle, with all enrolled (and randomized) patients included. The Kaplan-Meier product-limit approach was used.

Time to Disease Recurrence or Death

All randomized patients constituted the ITT Population, unless withdrawal of consent occurred after randomization but before the start of study treatment assigned.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer	NCT00171704	Hormone Sensiti...	Letrozole Tamoxifen	50 Years -	Novartis
A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer	NCT00171704	Hormone Sensiti...	Letrozole Tamoxifen	50 Years -	Novartis
A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer	NCT00171704	Hormone Sensiti...	Letrozole Tamoxifen	50 Years -	Novartis

Spots Global Cancer Trial Database for hormone sensitive resected primary breast cancer in postmenopausal women