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Answering the Unknowns of Taxanes for Breast Cancer During Pregnancy

Jim Kling

DISCLOSURES

SAN ANTONIO — Taxane exposure during pregnancy appears to be safe for mothers and offspring, according to a new retrospective cohort analysis. The findings shed light on a relatively unstudied topic. "Our cohort with 103 patients represents the most extensive study to date, and our main goal was to have homogeneous reporting of adverse events," Ana Ferrigno Guajardo, MD, said in an interview. She presented the results at the San Antonio Breast Cancer Symposium.

"Breast cancer during pregnancy is a very challenging clinical situation as the expected antineoplastic effects of treatment must be carefully balanced against potential detrimental consequences on the developing fetus," said Dr. Guajardo. She is a resident physician at Yale University School of Medicine.

Anthracycline-based chemotherapy agents are generally used during pregnancy because there is more safety data available for them, but some studies have shown that taxanes may have better efficacy in some clinical situations. "Cohort studies that have been done in the past [show] that taxane use is mostly deferred to the postpartum period, and we are not really sure of the impact that can have on survival in patients postponing treatment," said Dr. Guajardo.

There are potential safety concerns with taxanes because neonates lack the cytochrome enzymes to metabolize the drugs, which creates a theoretical risk of adverse effects due to prolonged activity. On the other hand, pregnant women metabolize taxanes faster, and there are placental barriers that can inhibit high molecular weight molecules like taxanes from reaching the fetus, according to Dr. Guajardo.

In addition to pregnancy outcomes, the researchers followed 28 infants, and found that 87% were found to be completely healthy, "so we were relatively reassured. But of course we think that there's a need for prospective studies that validate our findings regarding the safety taxanes," said Dr. Guajardo.

Although there is no direct comparison group, the findings correlate well with studies of the general population and other chemotherapy agents. "We have large cohorts with mostly anthracycline-based chemotherapy agents during pregnancy that we can compare our results to, and overall, we were reassured that the prevalence of complications that we found in our cohort was very similar or even lower to those reported in the literature with patients treated with anthracycline-based therapy," said Dr. Guajardo.

Compared with the general population, the team found higher rates of preterm births, neonatal ICU admissions, and premature membrane rupture, and infants that are small for gestational age. However, with the exception of the latter, all of these risks have been seen in pregnant women treated with other types of chemotherapy. "Perhaps it would be interesting to see if the incidence of small for gestational age neonates might be a bit higher in this population when compared to anthracycline-based therapy agents, but that does require a study that has a comparator group," said Dr. Guajardo.

The researchers recruited 103 women with an average age of 34 years from 10 centers in 6 countries: United States, France, Spain, Mexico, Italy, and Costa Rica. The great majority were also treated with anthracyclines during gestation, and nearly all (97%) were treated with paclitaxel. The live birth rate was 98%, and 43.4% were preterm, 24% were small for gestational age, 16% were admitted to the neonate ICU, and 12.5% had hyperbilirubinemia.

Obstetric complications included intrauterine growth restriction (9%), preterm premature rupture of membranes (5%), gestational diabetes mellitus (5%), hypertensive disorders (4%), and pregnancy loss (2%).

After the presentation, Virginia Borges, MD, professor of medical oncology at University of Colorado Anschutz Medical Center, served as a discussant.

"Highlights of this study [include] that it is an international cohort from over six countries with over 100 cases of women included specifically focusing on the use of paclitaxel. They demonstrated safe outcomes for the pregnancies and the mothers," Dr. Borges said during her presentation.

She went on to highlight several key points that physicians should consider when treating pregnancy-related breast cancer. "We want to achieve prepartum treatment wherever feasible to tackle that cancer before delivery of the child to prevent a pregnancy-related breast cancer from potentially turning into a postpartum breast cancer," she said.

"If the tumor is ER+/HER2-, we now see we can safely give anthracyclines and taxanes from 12 to about 35 weeks of gestation. We don't want to get too close to the delivery with chemotherapy. If a patient is HER2+, I prefer to give the anthracycline portion while the person is pregnant and then after delivery incorporate the taxane with the HER2 targeted therapies as there's some older data showing concurrent therapy looks a bit better than sequential. In triple negative breast cancer, again I prefer to give the anthracycline and delay the taxane and carboplatin to overlap with immunotherapy so we are getting the necessary synergy there as well," Dr. Borges added.

Dr. Guajardo has no relevant financial disclosures. Dr. Borges has consulted for SeaGen, Gilead, and AstraZeneca, and has received research funding from AstraZeneca, Gilead, Olema, and SeaGen.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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