System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ahead of print 1 citation

PubMed: 42522681 DOI: 10.1002/cpt.70404

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

Clin Pharmacol Ther

Authors: Rayan Kabirian, Floriane Jochum, Elise Dumas, Florence Coussy, Kevin Bihan, Bénédicte Lebrun-Vignes, Barbara Pistilli, Marc-Antoine Benderra, Lise Selleret, Laurent Chouchana, Fabien Reyal, Anne-Sophie Hamy, Paul Gougis

Affiliations

  • Residual Tumor & Response to Treatment Laboratory, RT2Lab, INSERM, U932 Immunity and Cancer, Institut Curie, Université Paris Cité, Paris, France.
  • Institut Curie Women's Cancers Institute, Department of Medical Oncology, Paris and Saint-Cloud, France.
  • Institute of Mathematics, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Regional Center of Pharmacovigilance, Department of Medical Pharmacology, Pitié-Salpêtrière Hospital, AP-HP Sorbonne Université, Paris, France.
  • French Pharmacovigilance Network. Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.
  • Clinical Investigation Center (CIC-1901), Institut National de la Santé et de la Recherche Médicale (INSERM) and Epidemiology in Dermatology and Evaluation of therapeutics), Université Paris Est Créteil (UPEC), Paris, France.
  • Institut Gustave Roussy, Department of Medical Oncology, Villejuif, France.
  • Institut Universitaire de Cancérologie, Sorbonne University, AP-HP, Tenon Hospital, Department of Medical Oncology, Paris, France.
  • Department of Obstetrics, Gynecology, and Reproductive Medicine, Tenon Hospital, AP-HP, Sorbonne Université, Paris, France.
  • Université Paris Cité, Inserm UMR-S 1343, Pharmacologie et évaluations des thérapeutiques chez l'enfant et la femme enceinte, Paris, France.
  • Department of Breast, Gynecological and Reconstructive Surgery, Institut Curie, Université Paris, Paris, France.
  • Sorbonne Université, Institut national de la santé et de la recherche médicale (INSERM), Assistance Publique - Hôpitaux de Paris (AP-HP), Clinical Investigation Center (CIC-1901), Department of Pharmacology, Pitié-Salpêtrière Hospital, Paris, France.
  • Sorbonne Université, Department of Medical Oncology, Assistance Publique - Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Institut Universitaire de Cancérologie, Paris, France.

Abstract

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.

MeSH

Pregnancy, Breast Neoplasms, Docetaxel, Neoplasms, Ear, Drug Therapy, Pharmacology, Breast, Therapeutics, Pharmacovigilance, Fetal Growth Retardation