Pilot Study of the Effect of Weight Loss on Breast Tissue and Blood Biomarkers in Women at Increased Risk for Breast Cancer

Primary Objectives

• The effect of bariatric surgery on Background Parenchymal Enhancement (BPE) on breast MRI through comparative analysis of images of women pre- and 1 year post-bariatric surgery.
• The effect of bariatric surgery on breast density as seen on standard four view mammograms by qualitative BIRADS category through comparative analysis of images of women pre- and 1 year post-bariatric surgery.

Secondary Objectives

• The impact of bariatric surgery on obesity associated immune markers in breast tissue by:

• Comparing cellular immune infiltrate components [B cells (CD 20), cytotoxic T cells (CD8), helper T cells (CD4), dendritic cells (CD11c), leukocytes (CD45), and monocytes/macrophages (CD68)] in breast tissue lobules of obese women pre-, 14 days post, and 1 year post bariatric surgery, and comparing these to normal breast tissue of lean women from the KTB
• Comparing the presence of crown like structures (CLS) in breast tissue of obese women at pre-, 14 day post-, and 1 year post - bariatric surgery, and comparing these also to normal breast tissue of lean women from the KTB.
• The effect of bariatric surgery on aromatase expression in breast tissue of obese women pre-, 14 day post-, and 1 year post-bariatric surgery, as compared to levels in breast tissue of lean women from KTB.
• The effects of bariatric surgery on other blood correlatives pre- and 14 day and 1 year post-bariatric surgery including: 1) PGE2, TNF alpha, IL1 beta, IL-8 and IL-10 in the inflammatory pathway; 2) adiponectin, leptin, insulin, IGF1, and IGFBP3 in the insulin pathway; and 3) estradiol, SHBG, E2, T and DHEAS in the hormonal pathway. These will also be compared to blood samples from lean women in the KTB.

Inclusion criteria

• Patients must be post-menopausal, defined as one of the following:

• Age over 60
• Prior oophorectomy
• No menstrual periods in the past 12 months without a medical procedure such as hysterectomy or uterine ablation
• FSH at castrate levels (> 40IU/L). Patients who do not meet criteria a-c (such as those under age 60 with prior hysterectomy but ovaries remain in place) will need to have an FSH level to confirm menopausal status prior to enrollment.
• Patients must have a BMI ≥ 30 as calculated by the formula:

Weight in pounds / height squared x 703 = BMI

A BMI of:

• 18.5-24.9 is considered normal;
• 25.0-29.9 is considered overweight;
• 30.0+ is regarded as obese.
• Patients must be planning to undergo primary bariatric surgery (no revisions).
• Patients must be willing to provide a core tissue biopsy at baseline and with repeat tissue collection after 2 weeks and 12 months post-bariatric surgery.
• Patients must be aged 18-75 years at the time of informed consent.
• Patients must be accessible for treatment, adverse event tracking and follow-up as determined by the treating physician.
• Patient consent and authorization for the release of health information must be obtained according to local institutional guidelines.

Exclusion criteria

• History of any malignancy except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years. History of breast cancer is not allowed.
• Concurrent or planned participation in randomized trials of weight loss or exercise interventions or trials targeting insulin, IGF-1 or their receptors. These interventions would interfere with the endpoints.
• Weight greater than 500 lbs at the time of imaging.
• Known allergy to gadolinium which is used for MRI contrast.
• History of life threatening allergic reaction to local anesthesia (lidocaine, xylocaine).
• For the purposes of invasive breast biopsies, women must not have received therapeutic anticoagulation in the 1 month prior to enrollment, and must have no medical reason why post-operative prophylactic anticoagulation could be held for 12 hours (i.e. atrial fibrillation, history of deep venous thrombosis).
• Prior history of breast irradiation.
• Use of chemopreventatives such as tamoxifen or raloxifene at any time prior to enrollment.