An Exercise RCT Targeting African-American Women With Metabolic Syndrome and High Risk for Breast Cancer

1. To assess the impact of exercise on biomarkers related to obesity, insulin-related
pathways, inflammation, hormones, and microRNAs.

2. The primary aim of this study is to compare the effect of 2 types of exercise
interventions (supervised and self-directed compared to control) on biological
parameters related to breast cancer development. It is important to understand if
participants in this study respond better to an exercise program they are able to engage
in on their own (self-directed) or if participating in an exercise program under
supervision is preferred. A study by Pinto utilized a home-based exercise program among
breast cancer survivors and commented that the home-based program has several advantages
including 1) mitigating transportation and scheduling difficulties, and 2) is less
expensive than supervised programs. Another study compared the effect of a supervised
exercise program to a self-directed exercise group and a control group on physical
functioning and health-related quality of life among breast cancer survivors and found
that participants in the self-directed exercise group improved their physical
functioning to a somewhat greater degree than the supervised group. The authors proposed
that one reason for this result could be attributed to the fact that the self-directed
program included many features thought to comprise effective home training including the
following: baseline fitness evaluations, written guidelines for home exercise, education
about pulse checking/heart rate guidelines, daily activity logs and bi-weekly telephone
calls by the exercise specialist. In the current study, we plan to employ features
similar to the self-directed exercise program in an effort to determine if the
self-directed group improves to a greater extent than the control group and better or
comparable to the supervised group. An added feature of the current study is that we
will administer a participant satisfaction questionnaire to assess each participant's
experience in their respective groups. This information will, in part, help us to plan
future studies. All participants will complete a baseline assessment prior to
randomization, as indicated in Table 1 in the attached grant proposal; follow-up
measures will also be conducted as indicated in that table. Participants will be
required to provide a medical clearance from their health care provider or a nurse
practitioner.

3. * Rationale and justification for study (i.e. historical background, investigator's
personal experience, pertinent medical literature, etc.): In the United States, breast
cancer is the most commonly diagnosed cancer in women, other than non-melanoma skin
cancer, and is the second most common cause of cancer deaths among women. Several risk
factors have been identified that increase breast cancer risk, some of which are
non-modifiable (e.g., age, family history, and race) and some of which are modifiable
(e.g., physical activity, body weight, dietary habits, and alcohol intake). Breast
cancer rates, which are increasing worldwide, parallel the increases in lifestyle
diseases including Type 2 diabetes, obesity, and metabolic syndrome (MetS). MetS
represents a cluster of risk factors associated with increased risk of cardiovascular
diseases, and includes several components individually related to breast cancer
etiology, i.e., central obesity, hypertension, hyperglycemia, and low high-density
lipoprotein cholesterol. However, recent studies have suggested that MetS is
underdiagnosed in African-American women because they are less likely to have decreased
HDL or increased triglycerides as compared to women of other races/ethnicities. Breast
cancer is hormone related and thus, the effects of established risk factors for the
disease, including obesity, differ before to after menopause. Among African-American
women, in whom MetS is very prevalent and breast cancer mortality rates are high, it is
hypothesized that intervening on MetS to improve the MetS profile may prove to be a
means to reduce breast cancer risk. The American Cancer Society (ACS) and the
International Agency for Research on Cancer of the World Health Organization now both
recommend regular physical activity as a strategy for women to reduce their risk of
developing breast cancer. Specific recommendations for breast cancer prevention, which
initially emphasized diet, are now focused on maintaining a healthy weight throughout
life by balancing caloric intake while increasing caloric expenditure via increased
physical activity levels, and losing weight if overweight or obese.

Obesity itself is a major public health problem and is associated with increased
postmenopausal breast cancer incidence and mortality. Our proposed pilot project compares two
exercise interventions: a supervised facility-based and a home-based exercise intervention to
a control group in African-American women with metabolic syndrome who are at high risk for
breast cancer (based on the CARE model).This study is a 6-month three-arm RCT to assess the
impact of the exercise interventions on biomarkers related to obesity, insulin-related
pathways, inflammation, and hormones. The specific aim of the proposed study is to compare
the impact of a supervised facility-based and a home-based exercise intervention on obesity,
metabolic syndrome and known breast cancer biomarkers in postmenopausal African-American
women with metabolic syndrome who are at increased risk of breast cancer.

Inclusion Criteria:

- Eligible participants should be female, African-American postmenopausal women between
the ages of 45 and 65 with waist circumference greater than 35 inches (88 cm), 5-year
invasive breast cancer risk is greater than 1.40% using the CARE model, and have at
least one of the following:

- elevated fasting glucose is greater than or equal to 100 mg/dL

- elevated blood pressure is greater than or equal to 130/85 mm/Hg. In addition, they
should also have a cell phone with texting capabilities, read and speak English,
reside in close proximity to, or can access the Navy Yard stop on the green line, can
provide meaningful consent, and medical clearance from a physician or nurse
practitioner.

Exclusion Criteria:

- -physical limitations that prevent participant from exercising

- premenopausal

- pregnant or planning to become pregnant within the next year

- history of cancer (except for non-melanoma skin cancer)

- have diabetes

- use anti-diabetic medication (including insulin)

- are currently enrolled in a physical activity and/or dietary clinical trial

- are on a weight loss program

- cannot commit to the intervention schedule