With increasing maternal ages worldwide, patients undergoing breast cancer treatment while pregnant is becoming a more common experience in clinical oncology, reported Hyman B. Muss, MD, professor of oncology and directory of geriatric oncology at the University of North Carolina in Chapel Hill. Dr. Muss spoke at the 33rd Annual Miami Breast Cancer Conference, held March 10–13 in Miami Beach, Florida.
“We’ll be seeing more of this,” he told attendees. “A lot of the issues that come up, are very tough to deal with.”
Pregnant women tend to present with breast cancer at more advanced stages of disease, “mainly because of breast engorgement during pregnancy,” Dr. Muss noted.
That can be associated with poor prognosis, but that’s not because of pregnancy’s effects on the underlying disease, he said.
“Survival looks similar for pregnant and non-pregnant women when adjusted for stage, phenotype, and treatment,” he explained. “It used to be said that survival was worse if a woman was diagnosed within the first year after delivery—but this has been shown not to be the case.”
Except for CT and positron emission tomography (PET) scans, most diagnostic workup procedures are safe during pregnancy. Ultrasound and mammography are safe during pregnancy, and the ionizing radiation dose from a radiographic mammogram is roughly equivalent to 7 weeks of background radiation levels, Dr. Muss noted. “But you have to reassure patients,” he added.
“Chest x-ray is safe with abdominal shielding until late in pregnancy, when the fetus becomes large,” he said.
However, CT/PET scans and radionuclide imaging for disease staging are not recommended during pregnancy.
“CT has just a tremendous amount of radiation,” Dr. Muss cautioned. “With lab work and ultrasound, you can be pretty certain you’re dealing with a patient who is not dealing with distant metastases.”
It is important to inform a pathologist that the patient is pregnant, he noted.
Chemotherapy pharmacokinetics can differ during pregnancy and after delivery, but those differences “don’t seem to translate into biological effects,” he noted. “Survival is similar if chemo is given before or after delivery; we don’t use pharmacokinetics data when determining treatment dose.”
Pregnant patients often feel considerable anxiety about the possible effects of treatment on their fetus. While there are important considerations, particularly in the first trimester of fetal development, treatment is frequently safer than feared, Dr. Muss said.
Chemotherapy can be “really scary,” he acknowledged. “But the only time it’s really contraindicated is in the first trimester,” when it carries a 14% risk of congenital malformations. (That statistic is based on experiences with methotrexate and older drugs, Dr. Muss noted.)
“After the first trimester, it’s relatively safe. By around [gestational] week 12 or so, the fetus has organs developed to the point where chemotherapy beyond this point is unlikely to cause major damage to development,” he explained. In later trimesters, the chemotherapy-associated risk of malformation is about 3%—the same as that seen in the general population.
Importantly, long-term follow-up with children who had prenatal exposure to chemotherapy shows “no effects of chemo on cognitive performance or how well they do in school,” Dr. Muss said.
Placental development isn’t complete until “about 40 weeks,” he noted, but placental trophoblast invasion is complete by week 20, he said.
“If you can wait until week 20 or later, it’s best to wait,” Dr. Muss advised. There exists “good safety data” for anthracyclines, taxanes, and cyclophosphamide during pregnancy, despite altered pharmacokinetics and a small risk to fetal development associated with transplacental drug transfer, he reported.
“No dose modifications are recommended,” he noted.
“Support drugs are pretty safe, too,” he said. It is still unknown whether NK1 inhibitors are safe during pregnancy, but 5-HT3 receptor antagonists are safe. Both types of agents are used for chemotherapy nausea management.
Steroids and dexamethasone in the first trimester may increase the risk of cleft palate, and methylprednisolone is preferred, he said.
Dr. Muss noted that granulocyte-colony stimulating factor (G-CSF) is probably safe.
Importantly, however, trastuzumab is “probably not safe” during pregnancy, Dr. Muss emphasized, because they are associated with an increased risk of premature birth.
Preferred regimens include doxorubicin/cyclophosphamide or epirubicin/cyclophosphamide every 3 weeks followed by weekly paclitaxel or every-3-week docetaxel, Dr. Muss said, adding that dose-dense regimens and G-CSF for higher risk cancers are preferred.
“There’s no need for 5-fluorouaracil,” he was quick to add.
It is important not to risk underdosing the patient, Dr. Muss said. “Maintain dose intensity, timing the last dose for before delivery. Try to plan to end chemo 2 to 3 weeks prior to delivery. Use published standard protocols.”
Patients are frequently advised to terminate their pregnancies for cancer treatment, but doing so is not associated with improved survival rates, Dr. Muss said.
The decision to keep or terminate a pregnancy during cancer treatment “rests on an informed discussion and is the patient’s decision,” he said.
Surgery is similar to options with non-pregnant patients, he said. “It’s always scary, but pretty safe. Doing flaps with mastectomy is difficult with this [pregnant] population. Mastectomy should not be recommended but sentinel lymph node biopsy is safe and accurate,” he said. Blue dye is “worrisome” because of an allergic reaction rate of 1%, he cautioned.