The development of BC during pregnancy is relatively uncommon occurring in 2.4 to 7.3 per 100,000 pregnancies. This life-threatening diagnosis results in a difficult dilemma for the woman as she navigates deciding on care for herself and her unborn child. Anthracycline-based treatment regimens are usually initiated following the first trimester and often exclude the use of taxanes (docetaxel and paclitaxel), which may improve outcomes compared with anthracycline monotherapy.

To explore the safety of taxanes for the treatment of BC during pregnancy, an international cohort study was conducted. The main objective of this study was to assess how often maternal and neonatal adverse events following exposure to taxanes during pregnancy occur and to evaluate obstetric outcomes.

This retrospective, multicenter cohort study involving 10 centers in six countries (including the United States, France, Spain, Mexico, Italy, and Costa Rica) enrolled patients aged 18 years or older with a diagnosis of invasive BC who had received taxane-containing chemotherapy regimens during pregnancy. Data were collected via a unified electronic case report form using Research Electronic Data Capture. Neonatal outcomes within the first 28 days of life and long-term adverse events were assessed. Only patients with a documented completion of pregnancy were included in the analysis.

he study examined the prevalence of preterm births (i.e., birth before Week 37 of gestation), intrauterine growth restrictions (i.e., fetal weight <10th percentile for gestational age), small for gestational age (SGA) neonates (i.e., birth weight <10th percentile for gestational age), and low birth weight (i.e., birth weight <2,500 g).

A total of 103 pregnant BC patients (median age at BC diagnosis: 34 years) who were treated with taxanes were included in the study. The median gestational age at the time of the mother’s BC diagnosis was 12 weeks (range: 1-34 weeks). Almost one-half of patients (47.5%) had stage II BC, and 30.7% had stage III BC.

Over 90% (91.1%) of women had been exposed to additional chemotherapeutic agents, including anthracyclines (90.1%) and cyclophosphamide (89.1%). In the majority of patients (92%), chemotherapy was started in either the second or third trimesters; however, eight patients were exposed during the first 14 weeks of gestation (7 were exposed between weeks 12-13.67). More than one-half (53.7%) of patients started taxanes in the third trimester. Although the median gestation age for initiation of chemotherapy was 16 weeks, for taxanes it was later at 28 weeks; the last taxane dose was administered at a median gestational age of 34 weeks. Almost all patients (96.1%) received paclitaxel, with the most common dosage weekly being 80 mg/m2 intravenously.

Among maternal outcomes, 6.8% of patients experienced grade III to IV adverse events, including hypersensitivity reactions, neutropenia, thrombocytopenia, and nausea and vomiting. Therapy had to be adjusted, temporarily interrupted, or permanently discontinued in about 12% of patients. One-half of these interferences with treatment were due to disease progression or hypersensitivity reactions.

The live birth rate was 97.9%. There were two miscarriages—one at 34 weeks’ gestation and one at 36 weeks’ gestation. In the latter case, there was pathological evidence of placental malperfusion. Both fetuses had been exposed to other chemotherapeutics in addition to taxanes.

Preterm birth occurred in 43.4% of patients. Of the 103 patients, data on obstetric complications were available for 94 and included most commonly intrauterine growth restriction (8.5%), preterm premature rupture of membranes (PPROM; 5.3%), and gestational diabetes (5.3%).

Data were available for 88 neonates exposed to taxanes in utero. Among these babies, the most common neonatal complications were hyperbilirubinemia (12.5%), respiratory distress syndrome (5.7%), and hypoglycemia (5.7%). Approximately 16% of neonatal were admitted to the neonatal ICU. Of the neonates for whom birth weight information was available (N = 76), over one-third (35.5%) had a low birth weight and almost one-quarter (24.3%) were SGA. Congenital malformations occurred in 2.2% of neonates (2 of the 93 for which the data were reported) of which one baby was exposed to multiple chemotherapeutic agents during the first trimester and the second child was exposed to numerous agents starting at 24 weeks of gestation. Malformations included pulmonary complications, kidney failure, and club foot.

At a median follow-up of 42 months, 85.7% of infants were deemed to be healthy based on data from 28 infants who were exposed to chemotherapy, including taxanes, during gestation. Four infants had long-term complications, including cardiac abnormalities, speech disorder following PPROM, renal dysfunction, hypertension, delayed growth, and bone issues (femoral anteversion), dental issues (incomplete temporary dentition), and ocular issues (retinopathy, epicanthus).

A systematic review also examined obstetric and neonatal outcomes following taxane exposure during pregnancy, although malignancies other than BC were also included; only 55.3% of patients had BC. The most common obstetric outcome was PPROM occurring in 11.4% of patients. The most common neonatal/perinatal outcomes occurring in more than one-half (54.5%) was being preterm followed by SGA in 30.3%. Perinatal complications included acute respiratory distress syndrome in 10.6% of neonates. A congenital malformation rate of 5.3% was reported and included bone and teeth formation, hip dysplasia, mitral valve stenosis, hypospadias, and multiple congenital malformations. Among the cases in which long-term (>1 year) data were available, 15.1% reported complications, including delayed speech, recurrent otitis media, and acute myeloid leukemia (2.0%); other complications occurred less frequently. The authors concluded that taxane use appears to be safe following the first trimester of pregnancy, with both obstetric and fetal outcomes similar to that seen in the general population.

Both of these papers provide pharmacists with insight and reassurance into the safe of the use of taxanes during pregnancy in patients with BC.

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