The negative association between pre-eclampsia and breast cancer risk may depend on the offspring's gender

Abstract

If the negative association between pre-eclampsia and subsequent breast cancer risk differs by gender, this would strengthen the hypothesis that factors intrinsic to the particular pregnancy may explain the association. The study included 701 006 parous Norwegian women with follow-up for breast cancer through the Cancer Registry of Norway. Breast cancer risk was lower in women with pre-eclampsia/hypertension in their first pregnancy, compared to other women (relative risk, 0.86, 95% CI, 0.78 -0.94), after adjustment for age at first birth, maternal birth year, length of gestation, marital status, and parity. The risk reduction was slightly greater if the woman delivered a son as opposed to a daughter (relative risks of 0.79 vs 0.94, P-value for interaction, 0.06), and if preeclampsia/hypertension was combined with pre-term delivery, these differences were more pronounced (relative risks, 0.62 vs 1.07, P-value for interaction 0.03). A subanalysis among 176 036 primiparous women showed a substantial risk reduction if the mother delivered a son (relative risk, 0.62, 95% CI, 0.47 -0.82), but essentially null if she delivered a daughter (relative risk, 0.92, 95% CI, 0.72 -1.18; P-value for interaction, 0.05). These results suggest that the effect of pre-eclampsia/hypertension may be attributed to factors associated with the particular pregnancy rather than an underlying biological trait of the mother. The stronger risk reduction related to having a son suggests a role for sex-dependent hormones in pregnancy.

Preeclampsia and maternal breast cancer risk by offspring gender: do elevated androgen concentrations play a role?

“…Preeclampsia was associated with a modest, non-significant maternal breast cancer risk reduction overall (maternal ageadjusted OR ¼ 0.87) that was similar to Vatten et al's (2007) overall estimate (RR ¼ 0.86), but a marked and significant risk reduction among women who delivered their first infant after the age of 30 years (adjusted OR ¼ 0.33) ( Table 1). The overall association of preeclampsia to subsequent breast cancer risk did not differ by offspring gender (adjusted OR ¼ 0.86 vs 0.90 for women who delivered a son or a daughter, respectively).…”

“…If the findings of Vatten et al (2007) and what we observe in the present study among older mothers of male preeclamptic pregnancies are real, characterising the hormonal profile of preeclamptic pregnancies by fetal gender and maternal age may provide additional insight into the mechanisms underlying the apparent protective effect of preeclampsia.…”

“…In their recent paper on preeclampsia/pregnancy-induced hypertension and maternal breast cancer risk, Vatten et al (2007) further characterise this association by offspring's gender, reporting a risk reduction with preeclampsia only when the mother carries a male fetus. The authors conclude that their findings are consistent with a protective effect originating with exposures incurred during the pregnancy rather than to an underlying biological trait of the mother, presumably because such factors would be unrelated to whether she conceives a female or male child.…”

Preeclampsia and breast cancer: The influence of birth characteristics

“…Interestingly, a recent meta-analysis reported a 14% reduced risk of breast cancer in women with a history of preeclampsia (HR ¼ 0.86 [95% CI 0.71e1.01]) [5]. Some studies suggest that such risk reduction is conferred to preeclamptic pregnancies with a male fetus only [6]. To further characterize the association between preeclampsia and breast cancer, in the current study we investigated the association overall and according to birth characteristics using nationwide Danish register-based data.…”

Pre-eclampsia and long-term maternal health

“…As women who smoke are less likely to develop pre-eclampsia, it has been suggested that women who had pre-eclampsia are less likely to develop cancer. 76 Systematic review and meta-analysis shows that this does not appear to be true. 25 Cigarette smoke may protect from pre-eclampsia through the action of carbon monoxide on the haemeoxygenase system, which in turn has been shown to lower production of sFlt-1 and sEng from endothelial cells and placental trophoblast.…”