The purpose of this second pilot study is to extend the feasibility demonstrated in NCT02963740 that the intervention achieves high levels of moderate to vigorous physical activity (MVI PA) and modulates risk biomarkers for breast cancer and cardiovascular disease in older, obese sedentary breast cancer survivors who are undergoing moderate calorie restriction.

All subjects participate in same intervention. Intervention consists of a 6-month structured weight loss program utilizing portion controlled meals and a prescribed level of graduated physical activity with an eventual goal of 200 minutes or more per week. The program will include twice weekly sessions with a trainer at a local YMCA, and weekly phone group sessions the first 3 months with transition to unsupervised exercise and less frequent group phone sessions the second 3 months.

Inclusion Criteria:

• Diagnosis of breast cancer having completed any cytotoxic chemotherapy, radiation or surgery at least 3 months prior to study entry (Cohort A2) OR No prior diagnosis of breast cancer but at high risk for development of breast cancer and participating in HSC 4601 (Cohort B)
• Body Mass Index (BMI) >30 kg/m2. Women with a BMI > 45 kg/m2 must be age < 60 and ability to perform physical activity must be confirmed
• By self-assessment, currently performing 60 minutes or less of purposeful exercise per week but able to walk at least 30 minutes on a level surface
• Possession of smart phone capable of running MyFitnessPal and Garmin Connect apps and willing to have diet and exercise data accessed by study personnel
• Access to a personal computer
• Live in the greater Kansas City Metropolitan Area
• Willing and able to perform moderate intensity exercise at least 5 days per week for 6 months. This consists of a supervised exercise intervention at one of the 15 YMCAs affiliated with our program for 2 days per week. Must be willing to perform unsupervised home exercise for the entire 6 months.
• Willing to participate in a weekly behavioral modification group phone call for first 3 months and every 2 weeks for the second 3 months
• Willing to participate in a controlled dietary intervention with portion controlled meals and partial meal replacements plus 35 servings of fruits and vegetables/week for 6 months and track food intake and exercise
• Blood tests (Cohort A2) must have been performed after completion of any breast cancer surgery, radiation therapy, or cytotoxic chemotherapy, with reasonably normal liver and renal function as well as a hemoglobin of 10 or higher and/or performed within a year of study entry

Exclusion Criteria:

• Use of metformin, insulin, steroids or prescription weight loss or anti-psychotic drugs within the prior 3 weeks
• Individuals with prior gastric bypass surgery or procedure that would impair absorption of nutrients
• Need for chronic immunosuppressive drugs
• Participation within the past 6 months on a structured weight loss program such as Weight Watchers®
• Physical impairments (bad hip, knees, feet, peripheral neuropathy) that would prohibit performing moderate intensity exercise at least 5 days per week.
• Any other condition or intercurrent illness that in the opinion of the investigator makes the subject a poor candidate for participation in the trial such as recent cardiac event
• Currently receiving investigational agents in a clinical trial