Biomarkers for Breast Cancer Risk in African American Women
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Observational

Summary: 
      Background:

      - At present, women do not have very accurate tests to inform of them of their personal risk
      of developing breast cancer. More information on the changes associated with both benign and
      cancerous breast lesions will help develop better risk information. Researchers have been
      looking at cells found in breast milk to study genetic changes related to breast cancer.
      However, most of these cell samples have been collected from white women. A new study wants
      to collect breast milk samples from African American women for further research. Comparing
      the results of genetic tests will help improve understanding of breast cancer risk in all
      women.

      Objectives:

      - To study genetic changes related to breast lesions, including breast cancer, in African
      American women.

      Eligibility:

      - African American women at least 18 years of age who are nursing a baby and who either have
      had or are being considered for a breast biopsy.

      Design:

        -  Participants will be screened with personal health questions.

        -  Participants will receive a box with sterile bottles for milk collection. They will
           collect two breast milk samples, one from each breast. They will also fill out a
           questionnaire about their medical history.

        -  The box with the samples and the questionnaire will be returned to the clinical center
           for study.

        -  After the box is returned, participants will be asked to provide a copy of the biopsy
           report for any breast biopsies they have had.

        -  There will be a followup phone call every year. Participants will provide health history
           information. This information will include whether they have been diagnosed with breast
           cancer in the previous year.
    

Detailed description: 
      Increasing evidence supports the importance of the role of pregnancy, lactation and
      post-weaning breast remodeling in the etiology of certain types of early onset aggressive
      breast cancers, including basal breast cancers, which are difficult to detect and treat and
      disproportionately affect African American women. Thus, improving methods for detecting or
      preventing early onset tumors is important from a clinical, public health and racial
      disparities perspective. Recent evidence indicates that analysis of breast milk during the
      postpartum period may advance the discovery of mechanisms and biomarkers related to risk of
      early onset, aggressive tumors. However, developing methods for collecting, processing and
      testing milk for biomarkers poses challenges.

      A research team co-led by Drs. Mark Sherman (NCI/DCEG/HREB) and Kathleen Arcaro (University
      of Massachusetts) has received an NIH Bench-to-Bedside award for a project entitled,
      Molecular Epidemiology of Postpartum Involution of the Breast: Development and Demonstration
      of Tools for Understanding the Postpartum Period in Relation to Risk for Early Onset Breast
      Cancer. The specific bench objectives of this project include:

        1. To develop improved methods for fractionating breast milk into epithelial cell rich and
           liquid components

        2. To optimize assays for DNA methylation, proliferation, apoptosis, p16 expression and
           telomere lengths using epithelial enriched breast milk fractions, and

        3. To develop assays for TGF-beta ligands, prolactin and sex -steroid hormone using liquid
           milk fractions.

      To achieve these objectives, NCI will initially work with fresh specimens that are being
      prospectively collected under the University of Massachusetts IRB-approved open protocol
      entitled Epigenetics and Breast Cancer Risk in African American Women , funded by the Avon
      Foundation for Women. Dr. Arcaro s lab is studying breast cancer risk and promoter
      hypermethylation in breast cells obtained from the milk of nursing women. They have analyzed
      breast cells from nearly 400 women and are continuing with long-term follow-up. However, the
      majority of the data has been from White women. Since disease risk factors differ between
      ethnic groups, it is important to test risk assessment methods on a wide population. The main
      purpose of this specific UMass study is to extend their findings of breast cancer risk to
      African American women. They plan to recruit 200 lactating African American women to
      participate in the breast milk study. This involves collecting questionnaire data, completing
      methylation analyses for eight genes, archiving milk and the remaining DNA for future
      studies, and annual follow-up.

      The key aims that we seek to address through the current protocol are related to objective
      (1) listed above: To develop improved methods for fractionating breast milk into epithelial
      cell rich and liquid components. Given that Dr. Arcaro has an IRB approved open protocol to
      collect fresh milk at University of Massachusetts, NCI can only pursue this collaborative aim
      (effectively within the timeframe of the bench-to-bedside award) in the context of this
      ongoing study. Specifically, the collaborative project that is the subject of this IRB
      application will assess the following aims through in vitro manipulation of fresh liquid milk
      collections: 1) the effects of modifying the initial rinse of epithelial pellets (rinse
      solution: saline vs. media; centrifugation speeds, temperature); 2) yields of cells and
      nucleic acids achievable via fractionation of milk using different types of immunomagnetic
      beads (coated with antibodies to remove leukocytes ( negative selection ) vs. coated with
      antibodies to remove epithelial cells ( positive selection ); 3) the relative preservation at
      room temperature at 24, 48 and 72 hours of milk suspended in cellular fixatives (e.g.
      formalin, Proclin) as compared to fresh milk without fixation; 4) the possibility that
      strategies 1 and 2 be combined. This project brings together specific experience and
      expertise at University of Massachusetts with regard to milk processing with technical
      knowledge from NCI, provided by Drs. Kopp, Heckman, Yang and Sherman. In particular, NCI
      Frederick and Dr. Heckman have successfully used immunomagnetic bead technology to purify
      epithelial cells from blood products and lactating mouse glands by removing leukocytes.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Volunteer milk donors (lactating women)
      
Keywords: Breast Cancer; Breast Milk; Epigenetics