Abstract P2-06-14: Utilizing Human Breast Tissue and Blood to Discern Novel Protective Properties of Early Pregnancy in Reducing Breast Cancer Risk

Abstract

Abstract Introduction: The incidence of breast cancer, the most common cancer in women, is very high in Western Countries and is increasing rapidly in the Third World. Yet, despite better screening, earlier diagnosis, and the development of new therapies, a cure for metastatic breast cancers remains an elusive goal. Since it is difficult to defeat breast cancer after it has occurred, finding new strategies to delay or prevent the development of breast cancer has been an important area for clinical and experimental investigations. Multinational studies have suggested that women who undergo a full-term pregnancy before the age of 20, with or without lactation, have about one half the risk of developing breast cancer compared to women who undergo their first pregnancy after the age of 35 or women who have never undergone a full term pregnancy. Thus, pregnancy at an early age protects against breast cancer development. This universal protective effect of pregnancy serves as a major clue and starting point in the search for new experimental strategies and novel biomarkers related to the prevention of breast cancer. Methods: Women were recruited who had never been diagnosed with breast cancer and fit in one of the following categories; 1) had their first child ≥25 years of age, 2) had their first child ≥35 years of age, and 3) a control group of women the same age as those in groups 1 and 2 but who have never given birth were recruited and provided a sample of breast tissue and blood simultaneously. These groups were categorized as early parous, late parous, or nulliparous and their RNA was isolated from tissue and whole blood. Human whole genome microarray analysis (Agilent) was performed to identify the genes that were persistently altered in expression due to early pregnancy. Results: The study of molecular alterations in breast cancer genes has succeeded in identifying some genetic mechanism of breast cancer development. We attempted to elucidate early pregnancy-related changes in genes in breast tissue and blood associated with resistance to breast cancer. Over 2200 genes were up-regulated 2 folds or more in the blood and breast of early parous women than late parous and nulliparous women. Approximately 5000 genes were down-regulated 2 folds or more in the blood and breast of early parous women compared to late parous and nulliparous women. Conclusion: These studies focused on the analysis of human breast tissue and blood to gain a deeper understanding of changes in parity associated with the protective effect of early pregnancy in women. From these altered gene expressions we have identified a gene signature for early parity. The persistently altered genes will be used as novel biomarkers to predict breast cancer risk and develop strategies to protect the breast from cancer development. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-14.