Maternal and Neonatal Complications Associated with Breast Cancer Systemic Treatments-A VigiBase Disproportionality Analysis Study.

Pregnancy-associated breast cancer (PrBC) presents therapeutic challenges. Understanding maternal-fetal safety of systemic anticancer therapies is critical. We performed a case/non-case disproportionality analysis using the WHO global pharmacovigilance database up to January 2024, to evaluate maternal-fetal outcomes associated with breast cancer (BC) systemic treatments. 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 with the two cornerstone cytotoxic classes, anthracyclines (doxorubicin, epirubicin) and taxanes (docetaxel, paclitaxel), assessed individually vs. other anticancer treatments. Secondary analyses assessed all BC treatments and trimester-specific risks. Of 3310 pregnancy-related reports, 1789 involved BC treatments. Median maternal age was 27.4 years (SD 13.8) vs. 29.3 (SD 11.7) in the comparator group. Adverse maternal-fetal outcomes were reported in 998 (55.8%) BC treatment reports vs. 470 (30.9%) in other anticancer treatments. Anthracyclines were associated with neonatal hematologic disorders (ROR = 1.7, 95% CI = 1.1-2.5) and intrauterine growth restriction (IUGR) (ROR = 2.1, 95% CI = 1.7-2.7). Paclitaxel was linked to sensory defects including congenital ear/ocular anomalies (ROR = 5.2, 95% CI = 2.2-12.3); all 8 cases involved platinum co-exposure (cisplatin: n = 5; carboplatin: n = 3), suggesting a platinum-mediated mechanism; and to 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) showed preliminary signals of increased congenital malformation risk, including face (ROR = 13, 95% CI = 2-79), and musculoskeletal malformation (ROR = 8, 95% CI = 1.1-60). This pharmacovigilance study identifies signals of disproportionate reporting of specific maternal and neonatal outcomes with BC treatments; these findings are hypothesis-generating and require confirmation in prospective registries.