Fetal Down Syndrome and the Risk of Maternal Breast Cancer

Background: Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone, proposed to be involved in the protective effect against breast cancer afforded to mothers who bear children. In comparison with normal pregnancies, Down syndrome pregnancies are characterized by further elevated hCG concentrations from late first trimester to the middle of the second trimester. This study aimed to compare the risk of breast cancer in women who gave birth to a child with Down syndrome (as a marker of elevated hCG exposure) with that of women who had only unaffected children. Methods: The study cohort included all mothers of live-born children in Norway and Sweden from 1967–1973 through 2004. During the study period, 54,063 women developed breast cancer; 5330 children with Down syndrome were born and 139 breast cancer cases were diagnosed in their mothers. We fitted Cox proportional hazards regression models to obtain relative risks of breast cancer, adjusted for risk factors for breast cancer, such as overall parity and age at births. Results: Mothers of Down syndrome children were at 23% increased risk to develop breast cancer (95% confidence interval = 4%–46%). The risk increase was limited to women who had a Down syndrome child after age 30, and seemed to be confined to women whose cancer was diagnosed before age 50. Conclusions: Study results do not support the hypothesis of a protective effect of elevated pregnancy hCG on maternal breast cancer.