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V. K. Gadi, K. E. Malone, K. A. Guthrie, J. L. Nelson
Abstract:
Background: Prior pregnancy is a well-recognized protective factor against the development of breast cancer. Recent studies have also demonstrated that pregnancy has the potential to establish small numbers of long-lived fetal-derived cells in the mother, a phenomenon known as fetal microchimerism (FMc). We tested a novel hypothesis that establishment of allogeneic FMc acquired during pregnancy results in improved immune surveillance against breast cancer. Methods: DNA extracts from peripheral blood specimens were obtained from a repository created for a population-based case-control study of risk factors for breast cancer in women 21 to 45 years old. Specimens were tested with quantitative PCR for a Y chromosome specific sequence. Male DNA is assumed to derive from prior pregnancy with a male fetus. (The approach permits comparison of cases to controls while recognizing that the overall prevalence of FMc is underestimated as FMc from female fetuses is not assessed.) Results: For final analysis, there were 100 parous women, 55 with primary invasive breast cancer and 45 randomly selected controls. FMc prevalence was 56% (25/45) and 27% (15/55) in controls and cases, respectively. The odds ratio for detection of FMc in controls vs. cases was 3.2 (95% CI=1.2-8.2; p=0.02) after adjustment for multiple variables in a logistic regression model. In addition, FMc concentrations were significantly higher in controls vs. cases (p=0.002). Median concentrations were 2 (0-78) and 0 (0-375) fetal genomes/100,000 maternal genomes in controls and cases, respectively. Breast cancer patients were older at the time of first birth and more likely to have used oral contraceptives than controls but were similar for other characteristics such as reproductive history and environmental exposures. Conclusions: Results suggest that the enigma of why some women are not afforded protection by pregnancy might lie in differences in the ability to acquire or maintain long-lived fetal cells potentially capable of allogeneic immune surveillance. Mechanistic studies of FMc in breast cancer are warranted. The impact of this work for patients is that it may result in the development of FMc- based therapies for prevention or treatment of breast cancer.
Associated Presentation(s):
1. Fetal microchimerism and breast cancer: a case-control study
Associated Presentation(s):