Does gender of offspring modify the time‐related effects of a pregnancy on breast cancer risk?

We have read with interest the report of Hsieh et al. (1999) about a possible modifying effect of gender of the offspring on the short-term influence of a pregnancy on maternal risk of breast cancer. In view of the heterogeneity of results among women below and above 40 years, Hsieh et al. (1999) proposed that the transient increase in risk may be less pronounced after giving birth to a boy than to a girl. Their conclusions were based on analyses of the total number of male and female offspring (with mutual adjustment) and classification of mothers having children of single or mixed gender (among multiparous women). We did not find any effect of gender of offspring on overall breast cancer risk in our prospective study of 802,269 parous Norwegian women, including 4,782 breast cancer cases in the age interval 20 to 56 years (Albrektsen et al., 1995a). In contrast with the results of Hsieh et al. (1999), however, we observed a tendency toward a reduced risk among women with several daughters only. We have now performed additional analyses to examine whether the time-related effect of a pregnancy, as reported previously for this cohort (Albrektsen et al., 1995b), differs by gender of the child. We also applied the procedure of Hsieh et al. (1999) with separate analyses among women below and above 40 years of age, to obtain directly comparable results. Our results are based on Poisson regression analyses of person-years at risk with age as the time scale (20 to 56 years) and with reproductive factors included as time-dependent covariates (monthly updating). Women who had ever experienced a multiple birth were excluded. Results from the age-specific analyses of total number of boys and girls are presented in Table I. In contrast with the results of Hsieh et al. (1999), the risk estimates for an increasing number of boys (assuming a linear trend) were very similar to those for girls among women below and women above the age of 40 years. However, a significant deviation from linearity emerged. In agreement with the results of Hsieh et al. (1999), the reduction in risk associated with 3 or more boys appeared to be more pronounced than that corresponding to 3 or more gi ls, in particular among women below the age of 40 years. It is difficult to interpret these risk estimates, however, since the reduction in risk associated with an additional child of a particular gender may depend on the order of birth. Our previous analyses (Albrektsen et al., 1994) showed a more pronounced reduction in risk for higher-order births. Moreover, the transient increase in risk appears to be more pronounced after the first than after higher-order births (Albrektsen et al., 1995b). Incidence rate ratios for mothers with 2 or more children having children of single or mixed gender did not differ significantly, and risk estimates were similar among women below nd above 40 years (Table II). Some heterogeneity in results appeared between strata of parity, though no statistically significant associations were found (results not shown). As in the study of Hsieh et al. (1999), there was a tendency toward a protective effect of having several boys before the age of 40, but this pattern was observed for women with 3 children only. In all other strata of parity and maternal age, women with girls only appeared to be at lowest risk. However, stratum-specific risk estimates were, in general, rather imprecise, in particular among women below the age of 40 years. None of these data-analytic strategies gives direct information about a potential heterogeneity in the time-related effects of a pregnancy according to gender of the child. Although women below the age of 40 years are more likely to have had a recent birth than older women, the younger age group