Lifestyle Intervention Study in Adjuvant Treatment of Early Breast Cancer

The primary objective of this trial is to evaluate the effect of the addition of a 2 year,
centrally delivered individualized, telephone-based lifestyle intervention focusing on weight
management to a mailed educational intervention on Disease Free Survival in post-menopausal
women with early stage breast cancer (hormone receptor positive), BMI ≥24-<40 kg/m2, who are
receiving standard letrozole adjuvant therapy. The telephone intervention will involve 19
phone calls, as well as mailings and a participant manual; women will be asked to lose up to
10% of their weight by reducing their caloric and fat intake (by 500-1000 kcal/day, 20%
calories fat) and increasing their moderate physical activity (to 150-200 minutes/week).
Secondary outcomes include overall survival, distant disease-free survival, weight change,
health-related quality of life (HRQOL), selected non-cancer medical events and biologic
factors (notably insulin). Approximately 2,150 women will be enrolled; follow-up will
continue until target event rates have been met (anticipated 4-6 years after completion of
the intervention). This sample size will provide 80% power (type 1 error 0.05 2-tailed) to
detect a hazard ratio (HR) for DFS of 0.74-0.76 in the weight loss intervention arm.

Inclusion Criteria:

- Post-menopausal woman with a diagnosis of invasive breast cancer (T1-3,pN0-2,M0) for
which definitive surgery was performed during the previous 36 months.

- On adjuvant hormonal therapy with letrozole at time of randomization (either as
initial adjuvant hormonal therapy or after a switch from tamoxifen or other hormonal
therapy).

- BMI ≥ 24 kg/m2.

- Medical, surgical or radiation oncologist agrees to subject participation in a diet
and physical activity program.

Exclusion Criteria:

- Life expectancy less than five years.

- Self-reported inability to walk at least 2 blocks (at any pace).

- Insulin requiring diabetes (telephone directed diet and physical activity changes
would be difficult in this population without close coordination with the treating
physician). Non-insulin requiring diabetics are eligible for the study.

- Serious digestive and/or absorptive problems, including inflammatory bowel disease and
chronic diarrhea that preclude adherence to the study diet.

- Cardiovascular, respiratory or musculoskeletal disease or joint problems that preclude
moderate physical activity. Moderate arthritis that does not preclude physical
activity is not a reason for ineligibility.

- Psychiatric disorders or conditions that, in the opinion of the investigator, would
preclude participation in the study intervention (e.g. untreated major depression or
psychosis, substance abuse, severe personality disorder).

- Patients on aromatase inhibitors other than letrozole at study entry.

- Known recurrence of breast cancer (local, regional or distant) at any time prior to
study entry.

- History of other malignancies except: adequately treated non-melanoma skin cancer,
curatively treated in situ carcinoma of the cervix, or other solid tumours curatively
treated with no evidence of disease for ≥ 5 years. Prior in situ cancer of the breast
is not a reason for exclusion.

- Patients not fluent in either English or French (spoken and written).

- Patient unwilling or unable to provide informed consent.