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

Primary Objectives

1. 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.

2. 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

3. 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.

4. 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.

5. 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 Twenty (20) total post-menopausal female patients are planned for
enrollment. Post-menopausal women are defined as: (1) those ≥ 50 years of age who had not
menstruated during the preceding 12 months or who had castrate follicle-stimulating hormone
levels (>40IU/L), (2) those who had undergone a bilateral oophorectomy.

1. Patients must have a BMI ≥ 30 as calculated by the formula:

Weight in pounds / height squared x 703 = BMI

A BMI of:

1. 18.5-24.9 is considered normal;

2. 25.0-29.9 is considered overweight;

3. 30.0+ is regarded as obese.

2. Patients must be planning to undergo primary bariatric surgery (no revisions).

3. 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.

4. Patients must have ECOG Performance Status of 0 - 1 within 28 days of registration
(see Appendix I).

5. Patients must be aged 18-75 years at the time of informed consent.

6. Patients must be accessible for treatment, adverse event tracking and follow-up as
determined by the treating physician.

7. Patient consent and authorization for the release of health information must be
obtained according to local institutional guidelines.

Exclusion Criteria

1. 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.

2. 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.

3. Weight greater than 500 lbs at the time of imaging.

4. Known allergy to gadolinium which is used for MRI contrast.

5. History of life threatening allergic reaction to local anesthesia (lidocaine,
xylocaine).

6. For the purposes of invasive breast biopsies, women must not have received therapeutic
anticoagulation in the 1 month prior to enrollment.

7. Prior history of breast irradiation.

8. Use of chemopreventatives such as tamoxifen or raloxifene at any time prior to
enrollment.