Benign Breast Disease: Toward Molecular Prediction of Breast Cancer Risk

Principal Investigator: HARTMANN, LYNN C
Institution Receiving Award: MAYO CLINIC
Program: BCRP
Proposal Number: BC013015
Award Number: DAMD17-02-1-0473
Funding Mechanism: Breast Cancer Center of Excellence Award
Partnering Awards:
Award Amount: $5,789,420.00


Better risk prediction is essential for early detection and prevention strategies. How can we better identify that 10' of women who will develop breast cancer?

Women who have had a breast biopsy with benign findings are currently defined as having benign breast ¿disease.¿ Benign breast disease (BBD) is very common, especially with increasing use of mammography, but we lack good studies clarifying just how common the condition is in the population. It is known that women with BBD have an increased risk of a later breast cancer and that breast cancer can occur in either breast. We believe that with current laboratory capabilities and new insights into the development of breast cancer, we can exploit BBD tissue samples for molecular risk prediction.

We have access to a group of 12,000 women who had breast biopsies with benign findings (i.e., BBD) at the Mayo Clinic between 1967 and 1992. With the completion of their follow-up for subsequent cancer events, we anticipate identifying 700 women out of the 12,000 who went on to develop breast cancer. These women will be cases in our study. Those cases will be matched to appropriate control women (those who have not developed breast cancer). The stored benign breast tissue from cases and controls will serve as the foundation for our laboratory studies.

There are hundreds of markers that we could potentially study as molecular risk predictors. We are basing our marker selection on a unifying hypothesis¿namely, that breast cancer development depends upon loss of control of many growth regulatory pathways through genetic changes and that these genetic changes occur because of widespread ¿instability¿ of the genome (or DNA). Such instability occurs early on and can be detected in stored BBD samples with a variety of techniques.

Recent evidence for our hypothesis has come from the laboratory of one of our Center co-investigators, Dr. Thea Tlsty, at the University of California, San Francisco (UCSF). She has perfected the technique of growing human breast epithelial cells in the laboratory. As normal breast epithelium from women undergoing reduction mammoplasty is grown long term, a small proportion of these cells escape from the usual proliferation barrier and as they do so, they acquire widespread genetic changes. We now wish to study this phenomenon in breast epithelium from women with BBD. We will also use gene-profiling techniques to see what genes are most involved in BBD in Caucasian women and African-American women.

Our Center is based in an established team of individuals at the Mayo Clinic who have demonstrated productivity in building and studying retrospective clinical resources with matching tissue components. To this Mayo team we bring Dr. Thea Tlsty from UCSF and Dr. Lisa Newman from Wayne State with recognized expertise in breast cancer in African-American women. The ideas and approaches incorporated in our Center will benefit from our partnership with a very strong advocacy team made up of Ms. Deb Collyar, President of Patient Advocates in Research; Ms. Char Plitman, Executive Director of the Minnesota Komen Foundation; Ms. Chris Norton, President of the Minnesota Breast Cancer Coalition; and Ms. Mary Amundsen, Mayo Clinic Cancer Center advocate.