Pierre Robin sequence associated with first trimester fetal tamoxifen exposure

Tamoxifen is a nonsteroidal antiestrogen used as the current adjuvant endocrine treatment of choice for premenopausal women treated for breast cancer and its potential for causing fetal harm during pregnancy remains inconclusive. While the evidence of tamoxifen's effects on humans in utero is minimal, animal studies have shown evidence of teratogenicity, hence the FDA's class D categorization of the drug. In 1994 Cullins et al. published a case report entitled "Goldenhar's Syndrome Associated with Tamoxifen Given to the Mother During Gestation." At the time of publication, the authors noted that the manufacturer of tamoxifen knew of two cases associated with tamoxifen administration which resulted in congenital craniofacial defects. Cullins' case of Goldenhar syndrome is also a craniofacial disorder and thus represented the third such case. We report on the fourth case of a tamoxifen-associated craniofacial anomaly. The mother became pregnant while undergoing tamoxifen therapy for breast cancer. A child with severe micrognathia and cleft palate was born. It is noteworthy that the two patterns of craniofacial malformations in tamoxifen exposed infants--Goldenhar syndrome in Cullins' et al. case and Pierre Robin sequence reported here--have also both been observed in isotretinoin exposed infants. While a larger spectrum of anomalies is characteristic of retinoic acid embryopathy, the specific craniofacial anomalies include facial asymmetry, microtia, micrognatha and U-shaped cleft of the secondary palate, that is, malformations seen in the two tamoxifen exposed infants. Therefore, it is conceivable that these two agents could produce comparable embryotoxic effects if they function in a like way during embryogenesis. While the majority of tamoxifen exposed infants are normal, the ascertainment of teratogenic effects from tamoxifen will best be determined by data from teratogen registries.