From OncoLog, October 2011, Vol. 56, No. 10
Treating Cancer in Pregnant Patients
By Bryan Tutt
Pregnancy is usually a joyous, hopeful time; a cancer diagnosis can be devastating. When pregnancy and cancer occur together, they present special challenges for patients and physicians. Fortunately, these challenges often can be overcome by a multidisciplinary approach to treatment.
“Cancer treatment is not incompatible with pregnancy,” said Andrea Milbourne, M.D., head of the Section of General Gynecology and an associate professor in the Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center. “The old idea that a pregnant patient has to choose between terminating the pregnancy and going without treatment isn’t true in most cases.”
According to Dr. Milbourne, cancer affects about 1 in 1,000 pregnant women. Breast cancer, leukemia, lymphoma, and malignant melanoma are the cancers that occur most often in pregnant women.
“The speculation is that breast cancer occurs more frequently during pregnancy than other cancers because many women are delaying childbearing until their 30s, when breast cancer incidence goes up,” said Richard L. Theriault, D.O., a professor in the Department of Breast Medical Oncology.
About 1 in 3,000 pregnant women are believed to have concurrent breast cancer.
Diagnosis and workup
Dr. Theriault said that most patients with concurrent pregnancy and breast cancer learn they are pregnant before they are diagnosed with cancer. Although women are sensitive to changes in their breasts during pregnancy and likely to notice any new lumps, these lumps are sometimes mistaken for blocked milk ducts or inflammation, which could delay correct diagnosis.
“The standard of care is the same for pregnant women as for nonpregnant women,” Dr. Theriault said. “Any time there is an abnormality in the breast that’s been there more than 2 weeks, it needs to be subjected to imaging of some type.” He said this usually includes diagnostic mammography and ultrasonography of the breast. Although the radiation dose from mammography is negligible, shielding is typically provided to protect the fetus.
If imaging suggests a mass may be cancer, a core needle biopsy is performed. If the initial ultrasound examination indicates lymph node involvement, a fine needle aspiration biopsy of the lymph nodes is done as well. Both these procedures can be done safely in pregnant women.
“In our population of pregnant women, 65%–70% have lymph node involvement at the time of diagnosis,” Dr. Theriault said. “If the lymph nodes are involved or if there is reason to suspect metastasis, we look for other organ systems that might also be involved—especially in women with symptoms like back pain or belly pain.”
Breast cancer is often found at later stages in pregnant women than it is typically found in nonpregnant women. “This may be due to younger age of the pregnant patient population and to changes in the breast occurring during pregnancy,” said Jennifer K. Litton, M.D., an assistant professor in the Department of Breast Medical Oncology. “We follow guidelines for evaluation of distant disease similarly in pregnant and nonpregnant women, but we modify the imaging due to the pregnancy.”
The common sites of breast cancer metastases are the same in pregnant women and nonpregnant women: lungs, liver, and bones. Chest radiography is used to screen for breast cancer metastases in the lungs; as with mammography, this procedure does not expose the fetus to dangerous levels of radiation, and shielding can be provided. Ultrasonography is used to check for liver metastases. Non–contrast-enhanced magnetic resonance imaging of the thoracic and lumbar spine is used to assess for bone metastases. Dr. Theriault said the accuracy of this imaging modality has been shown to be the equivalent of bone scintigraphy, which is avoided in pregnant women because it irradiates the fetus.
“We see the patient and stage the cancer, and then we determine the best treatment for the patient’s cancer while monitoring the fetus closely as well,” Dr. Litton said.
The most important concern about treating pregnant cancer patients is avoiding chemotherapy during the first trimester, when the risk of organ malformation in the fetus is greatest.
After the first trimester, pregnant women receive a standard chemotherapy regimen—5-fluorouracil, doxorubicin, and cyclophosphamide—similar to that given to nonpregnant women with breast cancer.
The use of taxanes typically is delayed until after the baby is delivered because of concerns that the high levels of cytochrome P-450 in pregnant women might increase the metabolism of these drugs, potentially limiting their effectiveness.
Likewise, trastuzumab, which is used to treat HER2-positive breast cancer, is given only after delivery. “We don’t want to give chimeric antibodies during pregnancy because there is concern that they could cross the placenta and cause fetal abnormalities or abnormal fetal development,” Dr. Milbourne said. Endocrine therapy with tamoxifen also is not given during pregnancy because it has been associated with birth defects.
Surgery can be done safely during pregnancy. As in nonpregnant patients, pregnant patients typically undergo mastectomy, partial mastectomy, or lumpectomy before or after chemotherapy.
“We prefer to use a team approach to treatment,” Dr. Theriault said. “We work with the Department of Clinical Cancer Genetics because most of these patients are in their 30s, so we want to look at their BRCA1 and BRCA2 risks. We communicate with our patients’ obstetricians and with the fetal medicine specialists at the Department of Maternal-Fetal Medicine at The University of Texas Health Science Center at Houston. Surgical oncologists see these patients early, and if we think radiation therapy will be needed after delivery, patients see a radiation oncologist early as well.”
Doctors prefer not to administer radiation therapy during pregnancy because of the proximity of the breast to the fetus. However, Dr. Litton said, “Radiation therapy for breast cancer is typically given after chemotherapy and surgery, and by that time, the baby has been delivered.”
The child’s health
“Our primary focus is treating the patient and her cancer, but we want a healthy baby as well,” Dr. Theriault said. “We always require an evaluation of the mother and the fetus by a maternal-fetal medicine specialist. Generally speaking, we want to have that done before every cycle of chemotherapy. That way, we can monitor the growth and development of the baby and we can plan for when delivery might occur.”
Dr. Milbourne said, “Depending on how long chemotherapy is given, delivery may need to be carefully scheduled, so communication between the treating obstetrician and the treating oncologist is very, very important. Many chemotherapeutic agents lower patients’ white blood cell and platelet counts, and this can be dangerous to the mother and the baby during delivery.”
Dr. Theriault was the principal investigator for a clinical trial in which pregnant women are treated for breast cancer and monitored to determine their long-term outcomes and the health of their children; Dr. Litton has since assumed the role of principal investigator. About 80 women have been treated since the trial began enrolling patients in 1989. “Our data show that pregnant patients do as well as nonpregnant patients and that the children’s health seems to be right on par with that of the general population,” said Dr. Litton. “We’ve had three children out of those 80 with congenital malformations, and in the general population the risk is 3%–4%.” In follow-up surveys, only allergies and eczema were more prevalent in the children of mothers treated in the trial than in the general population. And these differences could be the result of reporting bias.
Other cancers in pregnant patients
In addition to those with breast cancer, Dr. Milbourne sees pregnant patients with various other cancers. “Some of these cancers are found during pregnancy because pregnant women are under more intense scrutiny by physicians during pregnancy,” she said. “We’ve had patients whose leukemia was detected by blood work done during pregnancy.”
Dr. Milbourne said that the unique aspects of each patient’s pregnancy and cancer must be considered. For example, she said that women diagnosed with leukemia during the early trimesters of pregnancy usually do poorly because the low white blood cell and platelet levels associated with treatment can lead to infections or because high white blood cell levels in untreated patients pose a potential threat to the fetus. However, she added, “We’ve had a few who were treated successfully. We had one woman with chronic myelogenous leukemia who was treated with leukapheresis during pregnancy, and once the baby was delivered she was able to proceed with her definitive treatment.”
Cervical cancer is relatively rare in pregnancy; however, cervical dysplasia (precancerous changes in the epithelial cells of the cervix) is sometimes detected in pregnant women. “If a woman has an abnormal Papanicolaou test during pregnancy, we order a colposcopy, but if it doesn’t look like cancer, no biopsy is done until after the baby is delivered,” Dr. Milbourne said. If the cancer is in an early stage, it can be treated by surgery—a trachelectomy—without harm to the fetus. If the cancer is further along, radiation therapy and chemotherapy are the standard treatment. Because radiation therapy to the cervix would be lethal to the fetus, the pregnancy would need to be terminated before the treatment began.
In fact, radiation therapy for any type of cancer usually is avoided during pregnancy. “We have some patients who have had radiation therapy for head and neck cancers while pregnant with good results. But despite shielding to protect the fetus and despite the precision of these treatments, there is a certain amount of radiation scatter that could pose a risk,” Dr. Milbourne said.
Likewise, some pregnant patients with lymphoma have been successfully treated with radiation, but when possible radiation therapy for lymphoma is postponed until after delivery. In lymphoma and myeloma patients, many of the standard chemotherapeutic drugs can be given during the second and third trimesters of pregnancy. As in patients with breast cancer, treatment with monoclonal antibodies during pregnancy typically is avoided in these patients.
Cutaneous melanoma can be safely removed during pregnancy. Although surgery that does not involve the abdomen can be done safely in any trimester of a patient’s pregnancy, many doctors prefer to postpone surgical procedures until after the first trimester if possible because the risk of miscarriage is highest during the first trimester.
Ultimately, the decisions about cancer treatment during pregnancy rest with the patient. Her physicians need to discuss with her in detail the risks and benefits of all her cancer treatment options. “Some women will choose to terminate the pregnancy and focus on fighting their cancer; others will refuse any treatment until after the baby is born. We respect the patient’s decision,” Dr. Milbourne said. She added that treatment recommendations should include input from specialists involved in all aspects of the patient’s care. “Every patient needs to be looked at on an individual basis. If in doubt, get a second opinion; get a third opinion.”
For more information, contact Dr. Jennifer Litton at 713-792-2817, Dr. Andrea Milbourne at 713-745-6986, or Dr. Richard Theriault at 713-792-2817.