Breast Mammogram and Tissue Study
Breast Mammogram and Tissue Study
Background:

 Women whose mammograms show a lot of dense areas are more likely to develop breast cancer and
 to have cancers that are missed by mammograms.

 It is unclear why some factors lead to having dense breasts and why having dense breasts
 increases the risk of developing breast cancer.

 Objectives:

 To determine why some women s breasts look dense on mammograms.

 To determine what types of cells and tissues make up dense areas of breasts and why these
 tissues may be more likely to become cancerous.

 Eligibility:

 Women between 40 and 65 years of age who have not had breast cancer or received medicines or
 radiation for any type of cancer and who are scheduled to undergo a breast biopsy.

 Design:

 This study is conducted at the University of Vermont, in collaboration with the NCI.

 Participants undergo the following:

 -  Review of their medical records collected over the last 2 years by the Vermont
 Mammography Registry.

 -  Participation in a short telephone interview.

 -  Height and weight measurement.

 -  Testing of biopsy tissue collected for diagnosis or treatment.

 -  Future contacts regarding health status for up to 10 years, including review of
 additional mammograms, removed tissues, questionnaires and medical records collected by
 the Vermont Mammography Registry during the 10-year study.

 Participants may also undergo the following optional procedures:

 -  Provide a mouthwash sample for genetic testing.

 -  Provide a blood sample to test for markers of dense mammograms or breast cancer.
High breast density and aging are the strongest risk factors for sporadic breast cancer among
 women. Although glandular epithelium contributes to mammographic density, non-epithelial
 tissue components represent its major determinants: adipose tissue is radiolucent and fibrous
 tissue is dense. The hypothesis is that epidemiologic factors associated with elevated breast
 density alter the breast microenvironment (ME) (defined as all cells and structures
 surrounding luminal glandular cells including: myoepithelial cells; basement membrane,
 stromal fibroblast and myofibroblasts; endothelial cells and pericytes; inflammatory cells,
 collagens, matrix proteins, growth factors, hormones, and other biochemical components) in a
 manner that enhances dysregulated proliferation of breast epithelium and ultimately cancer.
 Specifically, the Investigators propose that epidemiologic factors that lead to increased
 exposure to hormones and inflammatory mediators alter the ME, leading to both increased
 breast density and cancer. The critical importance of the ME in carcinogenesis is supported
 by experimental and clinical data showing that epithelial abnormalities alone are generally
 insufficient for cancer development without concurrent changes in the ME. The primary aim of
 this pilot study is to demonstrate the feasibility of collecting the data needed to elucidate
 the biologic mechanisms that mediate the substantial breast cancer risk associated with high
 mammographic density. Specifically, the Investigators will develop, fine tune, and validate a
 complex cross-sectional study protocol to collect risk factor data and biological specimens
 (blood, buccal cells, tissue fluids, and tissue) required to discover mechanisms and
 biomarkers that link high mammographic density (as measured quantitatively using computerized
 methods) to breast cancer risk. They will enroll 250 women between the ages of 40 to 65 years
 undergoing a radiologically guided biopsy at the University of Vermont, the largest center
 within the Vermont Breast Cancer Surveillance System (VBCSS), to participate in this pilot
 study of mammographic density.
-  INCLUSION CRITERIA:

 Inclusion criteria for participation in the study are women, ages 40-65 years of age, who
 are undergoing a radiologically-guided biopsy (stereotactic- ultrasound-guided). We will
 NOT exclude subjects for current or past use of exogenous hormones; prior hysterectomy or
 salpingoophorectomy or presentation with a breast mass. Although most biopsies are prompted
 by a radiologic finding (typically abnormal calcifications or masses), some biopsies are
 performed for symptoms that are unassociated with a radiologic finding, such as nipple
 discharge, palpable mass, discomfort, etc. Elevated density per se is not a biopsy
 indication. ALL women referred for radiologically guided biopsy, irrespective of the
 indication, will be considered eligible for the pilot study.

 EXCLUSION CRITERIA:

 We will EXCLUDE women who have a prior history of breast cancer, have had an EXCISIONAL
 breast biopsy within one year, women who have implants in place, women taking tamoxifen or
 raloxifene for chemoprevention and women who have received non-surgical treatments for
 cancers of other organs.