Understanding How Early Pregnancy Protects Against Breast Cancer

Women who deliver a baby before the age of 20 have a 50% reduction in their lifetime risk for breast cancer.

But what causes this dramatically effective benefit of an early pregnancy?  At least two mechanisms appear to be involved, though, surely, more discoveries will be made to explain the protective benefit of early pregnancy on future breast cancer risk.  The first mechanism involves a protein, alpha fetoprotein, and the second involves breast stem cells.

Alpha fetoprotein (AFP) is made by the liver and the yolk sac of the growing fetus.  The high levels of estrogen made by the placenta over the course of a full-term pregnancy stimulate increased production of AFP.   Scientists have discovered that AFP inhibits the growth of breast cancer cells in culture and delays the growth of breast tumors by 30-50% studies of live animals..

Breast stem cells are the longest living cells of the breast.  Many scientists believe that breast stem cells are the primary source of all breast malignancies.  Breast stem cells are able to accumulate more mutations over the lifetime of the patient and, as a result, are the most susceptible to malignant transformation.  Pregnancy changes both the total number of breast stem cells – reducing them by half – and the genes expressed by the stem cells that remain behind after a full-term pregnancy.  One of the genes altered by pregnancy is Wnt 4, a gene that has been found to be particularly important in breast cancer formation.  Pregnancy reduces the amount of Wnt 4 made by cells in the breast.  Early pregnancy thus protects against breast cancer by reducing the total number of breast stem cells and reducing the expression of a particularly notorious breast cancer gene, Wnt 4.

The beneficial effect of an early pregnancy on lowering the incidence of breast cancer is dramatic:  a 50% reduction in lifetime risk is seen in women who deliver a child before the age of 20.  Several factors appear to be involved, including increased production of AFP, decreased expression of Wnt 4, and a 50% reduction in the total number breast stem cells.