More than one million women receive biopsy diagnoses of benign breast disease (BBD) in the U.S. each year, which creates an important need to develop risk prediction tools for these women. The parent grant related to this supplement seeks to improve risk prediction for women with BBD by assessing self-reported factors, mammographic density and tissue biomarkers. Evaluation of age-related lobular involution (ALI) of background lobules is a central component of the project, as these structures give risk to most BC precursors. Pregnancy reduces long-term breast cancer risk, but increases risk transiently for >20 years, which is proposed to reflect tissue remodeling and macrophage infiltration which accompany postpartum involution (PPI). Our parent grant focuses on assessment of ALI as a risk marker, but cannot adequately identify risk biomarkers related to PPI because most biopsies were performed many years post-childbirth. PPI is characterized by massive apoptosis of epithelial cells, macrophage influx, and increased expression of ?H2AX, a marker of DNA damage. We hypothesize that risk factors for PABC, such as failure to breastfeed, obesity and African American race, affect immune cell composition in normal tissues collected in the period following pregnancy and that some women develop a ?chronic mastopathy? that increases breast cancer risk. We will test this proposal by analyzing immune cell composition and ?H2AX in ?normal? breast tissues donated in the Komen Tissue Bank among parous and matched nulliparous AA and Caucasian women collected within 10 years of a live birth. Understanding the determinants of inflammation and DNA damage in breast tissues collected in the years following pregnancy could provide insights required to advance risk prediction and prevention, particularly for early onset lethal cancers. This project provides an excellent opportunity to develop Dr. Ogony?s expertise as an inter-disciplinary researcher focusing on racial disparities in breast cancer. Mentorship and resources at Mayo provide excellent support for this research and related training.
Postpartum involution (PPI) and age-related involution (ALI) are both associated with breast cancer. Our parent grant focuses on age-related lobular involution as a central component of the model to predict breast cancer risk after benign percutaneous biopsy, but cannot adequately assess postpartum involution because percutaneous biopsy samples are from women who are many years post childbirth. We request an administrative supplement to identify immune biomarkers associated with PPI, which may represent candidate biomarkers of breast cancer risk that can be applied to benign breast biopsies to predict progression.
