Abstract
BACKGROUND: Preeclampsia is frequently linked to reduced breast cancer risk. However, little is known regarding the underlying genetic association and the association between preeclampsia and mammographic density. METHODS: This study estimates the incidence rate ratios (IRRs) of breast cancer in patients with preeclampsia, when compared to women without preeclampsia, using Poisson regression models in two cohorts of pregnant women: a Swedish nationwide cohort (n = 1,337,934, 1973-2011) and the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA, n = 55,044, 1958-2015). To identify the genetic association between preeclampsia and breast cancer, we used logistic regression models to calculate the odds ratios (ORs) of preeclampsia in sisters of breast cancer patients, and in women with different percentiles of breast cancer polygenic risk scores (PRS). Linear regression models were used to estimate the mammographic density by preeclampsia status in the KARMA cohort. RESULTS: A decreased risk of breast cancer was observed among patients with preeclampsia in both the nationwide (IRR = 0.90, 95% CI = 0.85; 0.96) and KARMA cohorts (IRR = 0.75, 95% CI = 0.61; 0.93). Women with high breast cancer PRS and sisters of breast cancer patients had a lower risk of preeclampsia (OR = 0.89, 95% CI = 0.83; 0.96). Mammographic density was lower in women with preeclampsia compared to women without preeclampsia (-2.04%, 95% CI = -2.65; -1.43). Additionally, among sisters in the KARMA cohort (N = 3500), density was lower in sisters of patients with preeclampsia compared to sisters of women without preeclampsia (-2.76%, 95% CI = -4.96; -0.56). CONCLUSION: Preeclampsia is associated with reduced risk of breast cancer and mammographic density. Inherited factors contribute to this inverse association.