Background: The effect of pregnancy on the risk of breast cancer is not clear. We tested the hypothesis that the risk of breast cancer increases transiently after pregnancy but then falls to a level below that of age-matched nulliparous women.
Methods: We conducted a case-control study of a nationwide cohort in Sweden, using a computerized record linkage between the Cancer Registry and the Fertility Registry. The study subjects were women born from 1925 through 1960 who were resident citizens of Sweden at the time of the 1960 census. A total of 12,666 patients with breast cancer were compared with 62,121 age-matched control subjects. We used conditional logistic regression to estimate odds ratios for the development of breast cancer at different ages, according to maternal age at first delivery (in uniparous as compared with nulliparous women) and age at second delivery (in biparous as compared with uniparous women).
Results: Uniparous women were at higher risk of breast cancer than nulliparous women for up to 15 years after childbirth and at lower risk thereafter. The excess risk was most pronounced among women who were older at the time of their first delivery (odds ratio 5 years after delivery among women 35 years old at first delivery, 1.26; 95 percent confidence interval, 1.10 to 1.44). Women who had two pregnancies had a less striking increase in risk.
Conclusions: Pregnancy has a dual effect on the risk of breast cancer: it transiently increases the risk after childbirth but reduces the risk in later years. In women with two pregnancies, the short-term adverse effect is masked by the long-term protection imparted by the first pregnancy. A plausible biologic interpretation is that pregnancy increases the short-term risk of breast cancer by stimulating the growth of cells that have undergone the early stages of malignant transformation but that it confers long-term protection by inducing the differentiation of normal mammary stem cells that have the potential for neoplastic change.