Trial Information

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

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.