Pilot Study of the Effect of Weight Loss on Breast Tissue and Blood Biomarkers in Women at Increased Risk for Breast Cancer
Condition: Breast Neoplasms; Obesity
MeSH terms: Breast Neoplasms; Weight Loss
Study type: Observational

Summary: 
      This is a pilot, non-randomized, single institution, observational study investigating the
      effect of dramatic weight loss secondary to bariatric surgery on biomarkers of breast cancer
      in tissue and blood as well as on imaging in women at elevated risk for breast cancer. Twelve
      months after bariatric surgery, 50% of excess weight is generally expected. Eligible women at
      elevated risk for breast cancer who are already planning to undergo bariatric surgery will be
      consented to undergo imaging (MRI and mammogram), breast tissue biopsy, and fasting blood
      draw prior to bariatric surgery, approximately 14 days after bariatric surgery, and
      approximately 1 year after bariatric surgery.

      In parallel we will also be assessing 40 normal breast tissue specimens as well as blood
      samples from the Komen Tissue Bank (elevated risk but normal BMI) to establish a normal BMI,
      elevated risk control group for our study. The KTB samples will be matched for general risk
      of breast cancer (>20%), age, race and menopausal status.
    

Detailed description: 
      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.
    

Intervention name(s): Biopsy; Blood draw; Mammogram; MRI
Intervention type(s): Procedure; Procedure; Procedure; Procedure
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        20 total patients will be enrolled to the high risk/BMI > 30 cohort. 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.
      
Keywords: Biomarkers; Breast imaging