Pregnancy-related factors and risk of breast cancer in daughters: A systematic review and meta-analysis

Abstract

Background and aim: Pregnancy-related exposures have been proposed as potential risk factors for breast cancer later in life, but findings remain inconclusive. This study aimed to update evidence on the associations between the exposure to pregnancy-related factors occurring up to birth—maternal and paternal age, gestational age at birth, twin status, and maternal preeclampsia—and breast cancer risk in daughters. Material and methods: A systematic review and meta-analysis were conducted. Searches were performed in MEDLINE (via PubMed), Web of Science, and Scopus. We included observational analytical studies assessing associations between parental age, gestational age, twin status, and maternal preeclampsia and breast cancer risk in daughters, reporting effect measures with 95% confidence intervals (CI) or sufficient data for calculation. Study quality was assessed using the Newcastle-Ottawa Scale. A dose-response meta-analysis evaluated the effects of maternal and paternal age, while random-effects models assessed the effects of gestational age, twin status, and maternal preeclampsia. Heterogeneity was assessed using the I2 statistic and publication bias through funnel plots and Egger's tests. Results: Fifty-two studies met the inclusion criteria; 57.7% were high quality. Breast cancer risk increased with maternal age up to 30 years (I2 = 10.7%, P = .26). A possible association for paternal age (I2 = 33.8%, P = .08) disappeared in subgroup analysis (I2 = 1.0%). No associations were found for gestational age (pooled OR [pOR] 0.96, 95% CI 0.84 to 1.10), twin status (pOR 1.19, 95% CI 0.97 to 1.46), or maternal preeclampsia (pOR 1.08, 95% CI 0.71 to 1.64). Conclusions: Increased maternal age may influence breast cancer risk in daughters. No associations were found for paternal age, gestational age, or twin status; conclusions for maternal preeclampsia remain uncertain due to heterogeneity.