Maternal and neonatal complications associated with breast cancer systemic treatments: A VigiBase disproportionality analysis study.

626 Background: Pregnancy-associated breast cancer (PrBC) presents unique diagnostic and therapeutic challenges, with rising incidence due to delayed childbearing. Understanding maternal-fetal safety of systemic anticancer therapies during pregnancy is critical for informed treatment planning. Methods: We performed a case/non-case disproportionality analysis using VigiBase, the WHO global pharmacovigilance database up to January 2024, to evaluate maternal and fetal/neonatal outcomes associated with breast cancer (BC) systemic treatments. We included reports involving pregnancy, antineoplastic treatment during pregnancy, and cancer. The exposure group consisted of reports mentioning a BC treatment at any time during pregnancy. The primary outcome was the reporting odds ratio (ROR) of maternal-fetal complications in the BC treatment group involving at least one of the four main BC treatments: doxorubicin, epirubicin, docetaxel, paclitaxel, compared to other anticancer treatments. Secondary analyses assessed outcomes with all BC treatments and trimester-specific risks of the four main treatments. Results: Of 3,310 pregnancy-related reports, 1,789 involved BC treatments. Median maternal age was 27.4 years (standard deviation SD 13.8) in the BC treatment group versus 29.3 years (SD 11.7) in the other anticancer treatment group. Adverse pregnancy or neonatal outcomes were reported in 998 (55.8%) BC treatment reports versus 470 (30.9%) in other anticancer treatments. Anthracyclines were associated with neonatal immunodeficiency (ROR=11.0, 95%CI 3.2–40), hematologic disorders (ROR=1.7, 95%CI 1.1–2.5), infections (ROR=2.3, 95%CI 1.4–3.8), and pregnancy complications including IUGR (ROR=2.1, 95%CI 1.7–2.7) and hypertension/pre-eclampsia (ROR=1.9, 95%CI 1.2–2.9). Epirubicin was linked to craniofacial (ROR=7.6, 95%CI 2.5–23.5) and genitourinary malformations (ROR=6.3, 95%CI 2.1–18.9). Taxanes were associated with IUGR (paclitaxel ROR=2.8; docetaxel ROR=2.8), with paclitaxel linked to sensory defects (ROR=5.2, 95%CI 2.2–12.3) and hyperbilirubinemia (ROR=4.1, 95%CI 2.0–8.4), and docetaxel to neonatal neurologic disorders (ROR=3.6, 95%CI 1.4–9.3). First-trimester exposure (n=26) markedly increased risks of congenital malformations, i.e. face (ROR=13, 95%CI 2-79) and musculoskeletal malformation (ROR=8, 95%CI 1.1-60). Conclusions: BC treatments during pregnancy are associated with increased specific maternal and neonatal risks, with distinct drug- and trimester-specific variations. These findings highlight the need for individualized treatment planning and targeted fetal surveillance.