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Breast Cancer During Pregnancy Can Be Treated as in Nonpregnant Women

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Direction of Future Research

Future studies should address not just the toxic effects of chemotherapy during pregnancy but also the pharmacokinetics of cytotoxic agents in pregnant women, because the physiologic changes of pregnancy can greatly affect drug disposition, said Dr. Olivier Mir and Dr. Paul Berveiller.

"Whether doses should be increased in this population is uncertain because such increases could result in severe thrombocytopenia, neutropenia, and infection, with potentially devastating consequences for both mother and baby," they noted.

More research also is needed to determine whether the slightly increased fetal risks identified by Dr. Loibl and her colleagues could be minimized with better drug selection and dosing, they added.

Dr. Mir and Dr. Berveiller are in the Cancer Associated With Pregnancy Network, Paris. Dr. Mir is also in the department of medical oncology at Hôpital Cochin at the Université René Descartes, Paris. Dr. Mir reported ties to Roche, Pfizer, and Servier. These remarks were taken from their editorial comment accompanying Dr. Loibl’s report (Lancet Oncol. 2012 Aug. 15 [doi:10.1016/S1470-2045(12)70331-5]).


 

FROM THE LANCET ONCOLOGY

It appears that breast cancer diagnosed during pregnancy can be treated much the same as breast cancer diagnosed in nonpregnant women without substantially raising the risks to mother or child, according to a study published online August 16 in the Lancet Oncology .

This conclusion, from an observational study involving 447 European women included in registries of cancers diagnosed during pregnancy, must still be validated in other studies. But until then, the current evidence indicates that pregnancy outcomes are not significantly different between women who receive breast cancer chemotherapy during the second or third trimesters and those who wait until after delivery to start treatment, said Dr. Sibylle Loibl of the German Breast Group, Neu-Isenburg, Germany, and her associates.

In this study, infants exposed to their mothers’ breast cancer chemotherapy while in utero had slightly lower birth weights and slightly more complications than those not exposed to chemotherapy, but these differences were not clinically significant.

Breast cancer diagnosed during pregnancy is rare, estimated to occur in less than 1% of breast cancers in Europe. But its incidence is increasing in high-income countries due to the trend of women delaying childbirth until they are older, when breast cancer is more prevalent.

The German Breast Group established its Breast Cancer During Pregnancy registry in 2003 and expanded it to include cases in the Netherlands, the United Kingdom, Poland, Italy, and the Czech Republic in 2009. In the same time period, Belgium also established a registry of all cancers diagnosed during pregnancy. Dr. Loibl and her colleagues assessed outcomes in 447 cases from these registries in which women were diagnosed as having early (413 patients) or metastatic (34 patients) breast cancer while pregnant (Lancet Oncol. 2012 Aug. 15 [doi:10.1016/S1470-2045(12)70261-9]).

The median gestational age at diagnosis was 24 weeks (range, 5-40 weeks), and the median age of the women was 33 years (range, 22-51 years).

Data on chemotherapy were available for 368 women. Of these, 197 received chemotherapy while pregnant and 171 received it after delivery.

Overall, 1,187 cycles of chemotherapy were given, and 63% of these were given during pregnancy. The women received a median of four cycles (range, one to eight cycles) during pregnancy.

A total of 90% of those treated during pregnancy received an anthracyline; 8% received a combination of cyclophosphamide, methotrexate, and fluorouracil; and 7% received a taxane. None of the women received trastuzumab, endocrine therapy, or radiotherapy during pregnancy.

Women with early breast cancer who opted for chemotherapy during pregnancy tended to have more advanced disease, with more unfavorable tumor stage and nodal status, than did those who chose to begin chemotherapy after delivery. After the data were adjusted to account for this difference, the researchers found no significant difference between the two groups in disease-free or overall survival.

The estimated 3-year disease-free survival was 70.2% in women with early disease who underwent chemotherapy while pregnant and 74.3% in those who waited until after delivery. Similarly, the estimated overall 3-year survival was 84.9% in women with early breast cancer who underwent chemotherapy while pregnant and 87.4% in those who delayed chemotherapy until after delivery.

The estimated 5-year disease-free survival was 61.1% in women who had chemotherapy while pregnant and 64.4% in those who waited, and the estimated 5-year overall survival was 77% and 82.4%, respectively.

Data were available for 373 newborns, of whom 203 had been exposed to chemotherapy in utero and 170 had not.

Birth weight was slightly lower in the exposed than in the nonexposed infants, but this difference was judged to be "clinically irrelevant" because it didn’t affect the health of the babies, Dr. Loibl and her associates said.

Moreover, there were no significant differences between the two groups in major birth defects, infant height, Apgar scores, hemoglobin concentration, leukocyte counts, thrombocyte counts, or alopecia. And there was no significant difference in the proportion of infants discharged with their mothers (34% vs. 41%).

Adverse events occurred more often when chemotherapy was received during pregnancy (15%) than when it was delayed (4%). However, this difference was attributed to the higher rates of preterm labor and premature rupture of the membrane among exposed pregnancies. "Most complications were reported in babies who were delivered prematurely, regardless of exposure to chemotherapy," the investigators said.

The data were not adequate to determine why women who received chemotherapy had a higher rate of preterm delivery. Both physical stress and psychological stress may have played a role, and it is possible that women who received chemotherapy were more prone to infections that may have triggered labor.

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