In Utero Exposures and Breast Cancer: a Study of Opposite-Sexed Twins

It has been suggested that hormonal exposures in utero influence the risk of breast cancer later in life (1). Estrogens are well-established risk factors for breast cancer (2), and there is a pronounced association between birthweight and antenatal estrogen exposure (3). Several epidemiologic studies (4–6) have found that preeclampsia, a perinatal event characterized by low maternal estrogen levels, is associated with a decreased risk of breast cancer, but the results in different studies (6–8) of the association between birthweight and breast cancer risk are not entirely consistent. One possible reason for the divergent results could be the narrow range of antenatal estrogen exposure seen in singleton pregnancies. Twin pregnancies are characterized both by a broader range (9) and higher levels (9–11) of pregnancy estrogens. There is some evidence that these phenomena are even more pronounced in dizygotic twin pregnancies compared with monozygotic pregnancies (9,12), and most (5,13–16), but not all (8), studies of cancer risk among dizygotic twins show an increased risk of breast cancer. Dizygotic twins, therefore, constitute a suitable group for further studies of the association between antenatal hormonal exposures and breast cancer risk.