Impact of Obesity on the Efficacy of Endocrine Therapy With Aromatase Inhibitors

Study Overview
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Brief Summary
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To see the impact of obesity on the efficacy of adjuvant endocrine therapy with aromatase inhibitors in postmenopausal patients with early breast cancer in terms of: i) Locoregional recurrence ii) Distant metastases iii) Disease-free survival iv) Overall survival

Detailed Description
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The relationship between obesity and breast cancer is a complex one. Obesity is a risk factor for the development of breast cancer in postmenopausal women and has been linked to an increased risk of recurrence and decreased survival as compared to patients with normal weight. The hypothesis that led to this study is that the amount of total-body aromatization capacity indicated by body mass index (BMI). In postmenopausal women and in premenopausal women with ovarian suppression, the major source of serum estrogens is the fat tissue, in which precursors are metabolized to estrogens by the enzyme aromatase. Thus, an increase in BMI leads to an increase in total-body aromatization and, consequently, an increase in oestrogen serum levels, which impact on breast cancer. Taken together, this suggests that BMI may serve as a useful surrogate parameter for total-body aromatization and eventually may be a practicable tool to tailor aromatase inhibitors (AIs) therapy for individual patients. The study will include 360, postmenopausal patients with early breast cancer who have hormones receptor positive tumour as defined by the expression of oestrogen receptor (ER) and/or progesterone receptor (PR). Patients will be randomly assigned to receive tamoxifen 20 mg once daily or AIs (letrozole 2.5mg/ anastrozole 1mg/exemestane 25mg) once daily for five years. Patients with a tumour stage IB, IC, or II irrespective of nodal stage (<10 positive nodes) will be included. Weight and height will be taken at baseline for calculation of BMI according to the WHO criteria. The frequency of adverse events will be used to assess safety throughout the study. The primary end point will be disease-free survival (DFS). Secondary end points will be recurrence-free survival and overall survival (OS). The data will be analyzed for DFS and OS according to the BMI subgroups as well as two treatment arms (tamoxifen v AIs). The frequency of adverse events will be used to assess safety throughout the study.

Official Title
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Impact of Obesity on the Efficacy of Endocrine Therapy With Aromatase Inhibitors in Postmenopausal Patients With Early Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Tamoxifen
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: postmenopausal patients with breast cancer who have hormones receptor positive tumour as defined by the expression of oestrogen receptor (ER) and/or progesterone receptor (PR). patients with a tumour stage IB, IC, or II irrespective of nodal stage (< 10 positive nodes) Exclusion Criteria: premenopausal patients, ER/PR negative

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A- Letrozole<br>Aromatase inhibitor- letrozole 2.5mg once daily for 5 years | Drug: Letrozole<br>* Letroz, Femara, Letronat<br>* Other names: 2.5 mg once daily for 5 years;|
| Active Comparator: Arm B- Tamoxifen<br>Tamoxifen 20 mg once daily for 5 years | Drug: Tamoxifen<br>* 20 mg once daily for 5 years<br>* Other names: Canditam, Nolvadex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | Event in the form of locoregional recurrence, distant metastasis, cancer in the contralateral breast, second primary cancer, or death from any cause. | From date of random assignment to the first event during 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recurrence-free survival . | Disease specific mortality | From date of randomization until the date of first documented progression during 5 years | 
| overall survival (OS) | Till death due to disease/ other cause over an average of 5 years | From day of diagnosis till date of death from disease/ other cause over an average of 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, obesity, aromatase inhibitors, postmenopausal