Weight Loss Interventions in Treating Overweight and Obese Women with a Higher Risk for Breast Cancer Recurrence

Summary

Objectives

PRIMARY OBJECTIVE:
I. To compare the effect of a supervised weight loss intervention plus health education materials versus health education materials alone upon invasive disease free survival (iDFS) in overweight (body mass index [BMI] 27-29.9 kg/m^2) and obese (BMI >= 30 kg/m^2) women diagnosed with HER-2 negative, stage II and III breast cancer.

SECONDARY OBJECTIVES:
I. To determine the relationship between changes in weight and iDFS, and to explore interaction between the level of clinical benefit from weight loss and the intervention.
II. To evaluate the effect of a supervised weight loss intervention upon:
IIa. Overall survival.
IIb. Death from breast cancer.
IIc. Distant disease free survival.
IId. Breast cancer free survival.
IIe. Weight.
IIf. Body composition (as measured by waist and hip circumference).
IIg. Insulin resistance syndrome associated conditions – diabetes, hospitalization for cardiovascular (CV) disease.
IIh. Employment and work productivity.
III. To determine the impact of a supervised weight loss intervention on IDFS within subgroups of women with 1) hormone receptor positive breast cancer and 2) hormone receptor negative breast cancer.
IV. To determine the impact of a supervised weight loss intervention on IDFS within subgroups of 1) premenopausal women and 2) post-menopausal women.

OTHER OBJECTIVES:
I. Results of the primary analysis will be examined for consistency, while taking into account the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue.

CORRELATIVE SCIENCE OBJECTIVES:
I. To determine the impact of a supervised weight loss intervention upon:
Ia. Fasting insulin, glucose and homeostasis model assessment (HOMA).
Ib. Metabolic biomarkers, including adiponectin, leptin, IGF-1, IGFBP-3 and related factors.
Ic. Inflammatory mediators, including IL-6, TNF-alpha (a), hsCRP, and related factors.
II. To evaluate whether the benefits of the weight loss intervention are predicted by the following:
IIa. Baseline and change in levels of fasting insulin and glucose.
IIb. Baseline and change in other metabolic and inflammatory biomarkers (including adiponectin, leptin, IGF-1, IGFBP-3, IL-6, TNF-a, hsCRP).
III. To explore whether the benefits of the weight loss intervention are predicted by the following (A011401-ST1):
IIIa. Insulin and IGF-1 receptors (and related markers of signaling pathway activation) in breast tumor tissue.
IIIb. Crown-like structure breast in non-malignant breast tissue.
IV. To explore the relationship between gene expression in tumor tissue and the benefits of the supervised weight loss intervention (A011401-ST1).
V. To evaluate the prevalence and predictors of Clonal Hematopoiesis of Indeterminate Potential (CHIP) in BWEL participants and to explore the relationship between CHIP and outcomes including iDFS, breast cancer-free survival, OS, second cancers and CVD (A011401-ST1).
VI. To evaluate the presence and predictors of minimal residual disease (MRD) in BWEL participants who remain free of breast cancer recurrence at least 5 years after enrollment in BWEL (A011401-ST2).
VII. To explore the relationship between presence of MRD in BWEL participants who remain free of breast cancer recurrence at least 5 years after enrollment in BWEL and subsequent disease outcomes (A011401-ST2).

HEALTH BEHAVIORS AND PATIENT REPORTED OUTCOMES OBJECTIVES:
I. To determine the impact of a supervised weight loss intervention upon the following measures at months 6 (primary) as well as at 24 and 36 (secondary):
Ia. Weekly minutes of moderate and vigorous physical activity (primary).
Ib. Patient reported physical function (primary).
Ic. Daily caloric intake (secondary).
Id. Daily intake of servings of fruits and vegetables (secondary).
Ie. Proportion of patients meeting recommended levels of aerobic physical activity (secondary).
If. Minutes of self-reported physical activity (secondary).
Ig. General physical and mental health (secondary).
Ih. Anxiety, depression, fatigue, sleep, social roles, and pain (secondary).
Ii. Body image and clothing (secondary).
Ij. Cancer-treatment related and menopausal symptoms (i.e. cognition, endocrine symptoms, neuropathy, joint pain/stiffness) (secondary).
Ik. Circadian rhythm as measured by actigraphy for 1) amplitude and 2) shift in phase of circadian rhythm in relation to Earth’s day-night cycle (secondary).
II. To evaluate the relationship between changes in weight and changes in 1) physical activity patterns, 2) dietary intakes (secondary), and 3) circadian rhythm (secondary).
III. To use longitudinal data to explore the relationships amongst changes in weight, dietary intakes and minutes of physical activity and changes in patient reported outcomes including patterns of symptoms over time (exploratory).
IV. To evaluate whether baseline levels of patient reported outcomes are associated with adherence to physical activity, adherence to diet recommendations, or weight loss at 6 months; and whether 6-month and 24-month levels of patient reported outcomes are associated with adherence to physical activity, adherence to diet recommendations, or weight loss at 36 months. (exploratory).

BODY COMPOSITION SUBSTUDY OBJECTIVES (A011401-IM1):
I. To evaluate baseline body composition (total fat mass, visceral fat, subcutaneous fat and lean mass) and assess the incidence of sarcopenic obesity (high fat mass combined with low lean mass).
II. To evaluate the relationship between baseline body composition and changes in weight, metabolic biomarkers and inflammatory mediators in patients randomized to the weight loss intervention.
III. To explore the relationship between baseline body composition and invasive disease-free survival and overall survival in patients randomized to the health education only arm.
IV. To explore disparities in baseline body composition and assess the incidence of sarcopenic obesity between black and Hispanic BWEL participants versus non-Hispanic white (NHW) BWEL participants.
V. To explore the relationship between baseline body composition and invasive disease-free survival and overall survival by race/ethnicity.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive health education program brochures describing diabetes prevention, healthy dental habits, vision care, and skin care at study entry and at 1 year. Patients also receive a 2-year health magazine subscription. In addition, all patients are invited to join twice-yearly webinars/teleconferences focused on breast cancer and other health topics such as treatment updates in breast cancer, management of menopausal side effects, general cancer screening, etc. Patients also receive a twice-yearly study newsletter with study updates and other general breast cancer news.

ARM II: Patients receive health education program brochures describing diabetes prevention, healthy dental habits, vision care, and skin care at study entry and at 1 year, and a 2-year health magazine subscription. Patients also receive a telephone-based weight loss intervention over 30 minutes for 2 years consisting of: weekly calls for 12 weeks, calls every 2 weeks for 4-12 months and calls once per month for 13-24 months that focus on: weight loss, caloric restriction, and physical activity goals.

After completion of study treatment, patients are followed up every 6 months for 3 years and then annually until 10 years.