The fetal antigen hypothesis suggests that the lowered risk of breast cance
r in parous women may be afforded by the development of antibodies to fetal
antigens that are structurally similar to mammary cancer antigens. It has
previously been hypothesized that the likelihood of developing such antibod
ies may be higher among women who have had children with more than 1 partne
r. Utilizing information on parenthood and breast cancer available in natio
nwide Swedish registers, we undertook a case-control study nested within a
nation-wide cohort to address this issue. Number of partners fathering a ch
ild was categorized as 1, 2 and 3 or more. All analyses were restricted to
subjects with 2 or more births and encompassed a total of 20,881 women with
breast cancer and 111,989 control women. In an unadjusted analysis, the ri
sk of breast cancer was somewhat lower (odds ratio [OR] = 0.94, 95% confide
nce interval [CI] 0.89-0.99) in women who had had children with 2 different
partners compared with women who had had children conceived with the same
partner. After adjustment for parity, age at first birth and educational le
vel, however, the risk of breast cancer was slightly elevated (OR = 1.09, 9
5% Cl: 1.03-1.15). Among women who had had children with 3 or more differen
t men, the pattern was similar. The present results provide no support for
the hypothesis that greater antigenic exposure afforded by having children
with more than I man may reduce the risk of breast cancer. It remains possi
ble, however, that pregnancy may influence breast cancer risk through some
immunologic mechanism; further testing of the fetal antigen hypothesis may
require development of relevant laboratory measures. (C) 2001 Wiley-Liss, I
nc.