Figure 1.

When a mother (F0, black outline) is exposed to an environmental insult such as an unhealthy diet during pregnancy, her offspring's mammary tissues (F1 generation, fetus with black outline) and its already developing germ cells (orange)-which will give rise to the F2 generation-will be directly programmed and may cause intergenerational effects on F2 generation's breast cancer predisposition (fetus with orange color). Those environmental effects on breast cancer risk can be carried to subsequent generations (F3 generation and beyond, fetus wit green color) and represent true transgenerational epigenetic inheritance as they are transmitted through the F2 germline (green) which was not directly exposed to the initial environmental insult in the F0 generation. While evidence in humans is still lacking, animal studies support the idea that transgenerational epigenetic inheritance of breast cancer predisposition occurs (4, 48, 52).