Breast cancer risk in mothers of multiple births

Data from an international case-control study of breast cancer that was conducted in the 1960s were used to examine whether multiple births affect the risk of breast cancer in the mother. Among 2821 parous breast-cancer patients, 88 had had one or more multiple births, whereas among 8882 controls 247 had had one or more multiple births; the logistic-regression-adjusted odds ratio (OR) was 1.21, the 95% confidence interval (CI), 0.94 to 1.55. The OR was significantly elevated during the 15-year period following the latest multiple birth (1.76; CI, 1.12 to 2.75), but declined toward the null afterwards. A late first pregnancy imparted a substantially higher breast-cancer risk when it was multiple rather than singleton; the OR was 2.34 for a multiple and 1.48 for a singleton first pregnancy when the cutoff point was 30 years, and 4.58 and 1.57, respectively, when the cutoff point was 35 years. Since multiple pregnancies are characterized by higher levels of pregnancy estrogens, the results of this study would be compatible with the hypothesis that these hormones may be responsible for the transient increase in breast-cancer risk following a term pregnancy and, in particular, a multiple term pregnancy. The long-term reduction of breast-cancer risk is probably due to a different mechanism, most likely the terminal differentiation of susceptible mammary-gland cells.