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Although breast cancer diagnosed during pregnancy is a rare event, unfortunately its incidence is increasing. This rise is probably due to the fact that women in high-income countries are having children at an increasingly older age, which is associated with a higher probability of developing breast cancer. Despite this increase in the incidence of breast cancer during pregnancy, there is little evidence-based information on how to manage it, as, to date, most studies have been carried out in small cohorts. The first of these studies was published in 1999 by David Berry and colleagues, and included 24 patients with breast cancer treated during pregnancy using a standardized protocol at the MD Anderson Cancer Center. Now, nearly 15 years later, Sibylle Loibl and colleagues have expanded on those findings, aiming to corroborate in a much larger study the hypothesis that breast cancer treatment during pregnancy is safe for mother and child, and that pregnant women with breast cancer should not delay treatment.

“The project started in the early 2000s, when we had a couple of [pregnant] patients [with breast cancer] and came across the paper by Berry et al.” explains Loibl, “then we decided to hold an international consensus meeting and, because pregnant breast cancer patients cannot be randomized, we decided to set up a registry and collect data.” This registry included data from 447 patients of an median age of 33 years and an average gestational age at diagnosis of 24 weeks. Of the 447 registered patients, 205 women (197 of whom had been diagnosed with early stage breast cancer and eight of whom had been diagnosed with distant metastasis) received chemotherapy during the second and third trimesters of pregnancy, and 192 patients (171 of whom had been diagnosed with early stage breast cancer and 21 with distant metastasis) received chemotherapy after delivery. The chemotherapy regimen was mainly anthracycline-based, although some patients received a taxane or a combination of cyclophosphamide, methotrexate, and 5-fluorouracil.

“The primary aim was to look at the outcome of the children,” says Loibl. The researchers found that there was no difference in the rates of premature delivery—that is, delivery before 37 weeks of gestation—between patients who had been treated during or after pregnancy. Moreover, there were no differences in height, either, at the time of birth and at 4 weeks after delivery, in babies who had or had not been exposed to chemotherapy.

However, side effects, malformations, or newborn complications were more common in babies exposed to chemotherapy than in babies who had not been exposed (15% versus 4%). Interestingly, although birth weight after exposure to chemotherapy was very similar to that without exposure, after adjustment for gestational age, birth weight at delivery was affected by chemotherapy, although not by the number of chemotherapy cycles. “We were surprised to find that after chemotherapy [babies]are lighter. But this is usually not a problem,” comments Loibl, “we found that the women have more obstetrical complications, but we have so far no explanation for that.”

Did patients who received treatment while they were pregnant do better than those who waited until after delivery?

The main question is: is it worth the risk? Did patients who received treatment while they were pregnant do better than those who waited until after delivery? In women with early stage breast cancer, the estimated 5-year overall survival in the group of women receiving chemotherapy during pregnancy was 77% and 82.4% in women who received it after delivery. However, the authors affirm that these data do not suggest that initiation of treatment should be delayed: “Because more women in the group who started chemotherapy during pregnancy had involved lymph nodes, after correcting the statistical analysis for that it looked like there is a significant difference in favour of starting chemotherapy during pregnancy,” explains Loibl, “our intention was to demonstrate that there is no difference and that chemotherapy works during pregnancy because physiological changes have an impact on the distribution of the chemotherapy and might therefore be less active.”

Although some important questions remained unanswered—such as whether chemotherapy treatment might have long-term effects for those babies who were exposed to it in utero, or whether dosage should be increased in pregnant women according to weight changes—this study undeniably provides a better understanding of how to manage breast cancer during pregnancy.