Clinical trial NCT01758146: Impact of Obesity on the Efficacy of Endocrine Therapy With Aromatase Inhibitors
Official title: Impact of Obesity on the Efficacy of Endocrine Therapy With Aromatase Inhibitors in Postmenopausal Patients With Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Breast cancer
obesity
aromatase inhibitors
postmenopausal
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2013-01-01
Enrollment: 412
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease free survival
timeFrame: From date of random assignment to the first event during 5 years
Secondary outcomes:
measure: recurrence-free survival .
timeFrame: From date of randomization until the date of first documented progression during 5 years
measure: overall survival (OS)
timeFrame: From day of diagnosis till date of death from disease/ other cause over an average of 5 years
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Department of Radiotherapy, Post Graduate Institute of Medical Education & Research
Study officials:
affiliation: Post Graduate Institute of Medical Education & Research, Chandigarh, India
name: Dr Budhi S Yadav, MD
role: PRINCIPAL_INVESTIGATOR
References: