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

Post Graduate Institute of Medical Education and Research, Chandigarh

Status and phase: Unknown; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Tamoxifen; Drug: Letrozole

Study type: Interventional

Funder types: Other

Identifiers

NCT01758146

BMI

Details and patient eligibility

About

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

Full description

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.

Enrollment: 412 estimated patients

Sex: Female

Ages: 45 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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412 participants in 2 patient groups

Arm A- Letrozole

Experimental group

Description:

Aromatase inhibitor- letrozole 2.5mg once daily for 5 years

Treatment:

Drug: Letrozole

Arm B- Tamoxifen

Active Comparator group

Description:

Tamoxifen 20 mg once daily for 5 years

Treatment:

Drug: Tamoxifen