Pregnancy-related factors and breast cancer subtypes and prognosis: A systematic review and meta-analysis.

Abstract

Growing evidence suggests that pregnancy-related factors may influence long-term diseases, yet their role in breast cancer subtypes and prognosis remains uncertain. We evaluate current evidence on the association between pregnancy-related factors, including parental age, gestational age, breastfeeding, twin pregnancy, preeclampsia, and parental smoking, and breast cancer subtypes, as well as prognosis in daughters. We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines (PROSPERO: CRD42025619266). Searches were performed in MEDLINE (via PubMed), Web of Science, and Scopus in May 2025, and search alerts were activated. Study quality was evaluated using the Newcastle-Ottawa Scale. Random-effects and dose-response meta-analyses were conducted when at least two studies were available. Heterogeneity was assessed using Cochran's Q test and I² statistic. Nine studies met inclusion criteria (six cohort and three case-control studies); 78% were of high quality. Meta-analyses revealed no significant associations between gestational age and breast cancer subtypes [ER+: pRR= 1.01 (95% CI, 0.87 - 1.18; I2 =0.0%); ER-: pRR= 1.04 (95% CI, 0.74-1.46; I2 =17.8%)]. For mortality, a dose-response meta-analysis suggested a non-significant increasing risk trend for maternal age at delivery (I2 = 55.0%). The heterogeneity was not resolved in the meta-analysis for the association between breastfeeding and breast cancer subtypes (I2 > 40.0%) or for the associations between mortality and paternal age (I2 = 41.0%) or gestational age (I2 = 88.9%). In conclusion, the evidence for an association between pregnancy-related factors and breast cancer subtypes or prognosis in daughters is limited and heterogeneous, precluding firm conclusions.