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Chemotherapy during pregnancy did not elevate risk for birth defects
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Infants exposed to chemotherapy in utero did not exhibit greater clinically significant risk than those infants whose mothers did not receive chemotherapy while pregnant. However, infants exposed to chemotherapy in utero had a lower birth weight at gestational age than unexposed infants and additional complications, most likely related to premature delivery.
“The incidence of breast cancer during pregnancy is increasing, likely due to women in high-income countries having children at an increasingly older age, with the probability of developing breast cancer increasing with age,” Sibylle Loibl, MD, and colleagues of the German Breast Group in Neu-Isenburg, Germany, wrote. “[However] because of the low incidence of breast cancer during pregnancy and despite an increasing number of studies, evidence-based management of breast cancer during pregnancy is not possible because most information is based on small cohorts.”
To determine the safety of breast cancer treatment to both mother and child during pregnancy, the researchers enrolled 413 patients with early breast cancer in a multicenter registry cohort study for breast cancer during pregnancy. The cohort study was later expanded to other countries — including the Netherlands, the United Kingdom, Poland, Italy and the Czech Republic.
All patients diagnosed with breast cancer during pregnancy were eligible for registration, independent of outcome of the pregnancy and the type/timing of breast cancer treatment, with no age restrictions.
From April 2003 to December 2011, 197 (48%) of the enrolled women received chemotherapy during pregnancy with a median of four cycles (range one to eight). In addition, 178 patients received an anthracycline, 15 received cyclophosphamide, methotrexate and fluorouracil, and 14 received a taxane.
According to study results, birth weight was affected by chemotherapy exposure after adjustment for gestational age (P=.018), but not by number of chemotherapy cycles (P=.71). There was no statistical difference observed between the two groups for premature deliveries before the 37th week of gestation.
“In the general population, about 10% to 15% of infants are born preterm, but in our study, 50% of women with breast cancer delivered preterm, with 23% delivering before the 35th week of gestation,” Loibl said in a press release. “More complications were reported in the group of infants exposed to chemotherapy than in the group not exposed to chemotherapy. However, most complications were reported in babies who were delivered prematurely, irrespective of exposure to chemotherapy.”
The researchers observed that 40 (10%) of 386 infants had adverse effects, malformations or newborn complications, which were more common in infants born before the 37th week of gestation (16%) than in those born in the 37th week or later (5%; P=.0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (15% vs. 4%; P=.00045).
There were two incidents of infant mortality: both were exposed to chemotherapy and delivered prematurely, but both deaths were thought not to be related to treatment.
Median DFS for women with early breast cancer was 70.6 months (95% CI, 62.1-105.5) in patients starting chemotherapy during pregnancy and 94.4 months (95% CI 64.4-not yet reached) in women starting chemotherapy after delivery (unadjusted HR=1.13; 95% CI, 0.76-1.69).
“Our findings emphasize the importance of prioritizing a full-term delivery in women who undergo chemotherapy while pregnant,” Loibl said. “Illness and mortality in newborn babies is directly related to gestational age at delivery. This is an important clinical message because the decision to deliver the fetus preterm is often taken without medical indication. Our work suggests that treating patients with breast cancer while pregnant is possible, and there is no need to interrupt the pregnancy or receive inferior therapy.”
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Stephen Y. Chui, MD
Breast cancer occurring simultaneously with pregnancy is rare. However, my experience has been that when a cancer diagnosis is made in the midst of what should be the joyful occasion of child-bearing, the initial reactions range from sadness to terror.
Recommendations for treating breast cancer during pregnancy have largely been based upon the series of patients published by the group from MD Anderson in 2006 – this data showed that anthracycline-based chemotherapy could be delivered to during the second and third trimester of pregnancy with minimal risk to the development of the fetus. The German Breast Group Breast Cancer During Pregnancy Registry provides us with additional convincing data showing that breast cancer therapy, including chemotherapy, can be delivered to safely to pregnant mothers after the first trimester with good outcomes for the unborn children, and the expected breast cancer outcomes for the women receiving this treatment.
While the moral principles that guide our medical practice rightly puts the health of the mother above that of the unborn child, it is reassuring that a diagnosis of breast cancer does not imply that a simultaneous pregnancy should automatically be terminated in order to deliver therapy to the mother. This information helps us to be better equipped to help counsel treatment decisions in these unfortunate and challenging circumstances.
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