Cancer Treatment During Pregnancy Feasible

Roxanne Nelson

August 16, 2012

August 16, 2012 — Women with breast cancer can be treated during pregnancy without putting fetal and maternal outcomes at substantially increased risk, according to an international study published online August 16 in the Lancet Oncology.

However, the researchers did find that infants exposed to chemotherapy in utero had a lower birth weight than those not exposed. They also had more complications, but the differences between the 2 groups were not clinically significant.

Importantly, there were no major birth defects reported. The researchers, led by Sibylle Loibl, MD, from the German Breast Group in Neu-Isenburg, also note that because none of the infants in the study were exposed to chemotherapy during the first trimester, complications were most likely related to premature delivery.

"Our findings emphasize the importance of prioritizing a full-term delivery in women who undergo chemotherapy while pregnant," said Dr. Loibl in a statement. "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," she explained.

Women who delayed treatment until after delivery did not appear to have worse outcomes than those who underwent treatment while pregnant. There were no significant differences in disease-free survival or overall survival between the 2 groups.

Questions Unanswered, More Data Needed

Even though the results of this study suggest that anthracycline-based chemotherapy is feasible in the second and third trimesters of pregnancy, the optimum use of cytotoxic drugs in pregnant women remains undefined, according to an accompanying comment. This is particularly the case for drug selection, dosing, and dose intensity, write Olivier Mir, MD, and Paul Berveiller, MD, both from the Cochin Teaching Hospital in Paris, France.

Drs. Mir and Berveiller point out that although this study confirms findings from previous studies about the safety profiles of epirubicin and doxorubicin in pregnancy, it adds little information about taxanes.

The calculation of chemotherapy doses is also unclear in pregnant women, they write; "seemingly, no published data support the use of dosing based on body surface area in this population."

It is not known whether actual body weight or body weight prior to the pregnancy should be used to calculate body surface area, Drs. Mir and Berveiller note.

Another issue is physiologic changes during pregnancy, which can greatly affect drug disposition. Changes in albuminemia and the distribution and clearance of drugs are seen in the second and third trimesters.

"Finally, few studies...have assessed long-term outcomes of chemotherapy during pregnancy," write Drs. Mir and Berveiller. "Further clinicopharmacological studies are needed to determine whether the increased fetal risks shown [in this study] could be minimized with optimized drug selection and dosing."

Need to Terminate Varies With Cancer

Because cancer during pregnancy is a rare occurrence (incidence ranges from 0.02% to 0.10%), there is a scarcity of research to guide women and their physicians on treatment.

However, 2 previous studies found that pregnancy does not have a deleterious effect on the prognosis of gynecologic or breast cancers, and that pregnancy should be preserved whenever possible (Lancet. 2012; 379:558-569, 570-579). In addition, those studies found that prognosis and treatment success depends on the individual patient, and that it is possible to provide standard therapy to the mother while safeguarding the fetus.

Hematologic cancers represent more of a dilemma. These malignancies pose a substantial risk to both mother and fetus, and pregnancy termination is often advisable in the early stages, which will allow for the delivery of adequate therapy, according to another study (Lancet. 2012;379:580-587). Treatment largely depends on the type of malignancy and its characteristics. In some cases, such as with indolent lymphomas, treatment can be delayed without jeopardizing the health of the mother.

"But acute leukemia, being a life-threatening disease, should be immediately treated," Benjamin Brenner, MD, director of the Department of Hematology and Bone Marrow Transplantation at the Rambam Health Care Campus, Haifa, Israel, one of the authors of the study on hematologic cancers, previously told Medscape Medical News. "Therefore, early termination of pregnancy is required to address the need for urgent and optimal chemotherapy."

Some Risks Observed

In their study, Dr. Loibl and colleagues enrolled women from 7 European countries who were diagnosed with breast cancer while pregnant. A total of 447 patients were registered from April 2003 to December 2011, and 413 were diagnosed with early breast cancer. Median age of the mother at diagnosis was 33 years (range, 22 to 51 years), and median gestational age of the fetus was 24 weeks (range, 5 to 40 weeks). The primary end point was fetal health for up to 4 weeks after delivery. The registry is ongoing.

In this cohort, 197 women (48%) were treated with chemotherapy during their pregnancy, with a median of 4 cycles — 178 received an anthracycline; 15 received cyclophosphamide, methotrexate, and fluorouracil; and 14 received a taxane.

After adjustment for gestational age, the researchers observed that birth weight was affected by in utero exposure to chemotherapy (P = .018), but not by the number of chemotherapy cycles received by the mother (P = .71). There was no statistical difference in premature deliveries before 37 weeks of gestation between women who received chemotherapy and those who did not.

Of 386 infants, 40 (10%) experienced adverse effects, malformations, or newborn complications. These events were more common in premature infants (born before the 37th week of gestation). Adverse events were more common in infants exposed to chemotherapy than in those not exposed (15% vs 4%; P = .00045).

Of the 413 women who were diagnosed with breast cancer before the 28th week of gestation, 6% delayed chemotherapy until after delivery.

For women diagnosed with early breast cancer, median disease-free survival was 76.3 months; median overall survival has not yet been reached.

Median disease-free survival was 70.6 months (95% confidence interval [CI], 62.1 to 105.5) for women receiving treatment during pregnancy and 94.4 months (lower 95% CI, 64.4; upper 95% CI, not yet reached) for those who delayed treatment (unadjusted hazard ratio, 1.13; 95% CI, 0.76 to 1.69; P = .539).

Estimated 5-year disease-free survival was 61.1% for women receiving treatment during pregnancy and 64.4% for those who delayed treatment. Estimated 5-year overall survival rates were 77.0% and 82.4%, respectively.

Of the 65 women for whom data were available on obstetrical complications and systemic therapy, 19% experienced adverse effects (obstetrical or nonobstetrical). The occurrence of these events was more common in women who received chemotherapy during pregnancy than in those who did not (27% vs 10%; P = .0001).

In addition, symptoms of preterm delivery, which included preterm labor and premature rupture of membranes, were significantly more common in women receiving chemotherapy during pregnancy (14 vs 3; P = .012).

The study was funded by the BANSS Foundation and the Belgian Cancer Plan, Ministry of Health, Belgium. The study authors and Dr. Berveiller have disclosed no relevant financial relationships. Dr. Mir reports being an advisory board member and consultant for Roche, Pfizer, and Servier.

Lancet Oncol. Published online August 16, 2012. Abstract, Comment

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