Unexpected Complications: Treating Cancer during Pregnancy
Trina Pockett of Fortuna, CA, was 23, the mother of a 2-year-old, and pregnant with her second child when she noticed a lump under her collar bone. The lump wasn't painful, so for a while she ignored it. When the lump didn't go away, she showed it to her doctor, who ordered an emergency biopsy.
The diagnosis was devastating. She had Hodgkin lymphoma, an immune-system cancer that is one of the most commonly diagnosed cancers in young adults. Because the cancer had already spread to her neck, chest, and stomach, her doctors advised starting chemotherapy immediately.
Pockett suddenly found herself a member of an extremely small club: the estimated 3,500 women in the United States who each year receive a diagnosis of cancer during pregnancy. For each woman and her doctors, the diagnosis creates an exquisite dilemma: delaying treatment may risk her life, but proceeding with therapy may risk harming her unborn child.
No Rigorous Studies
Cancer—most commonly breast cancer, cervical cancer, lymphoma, and melanoma—occurs in about one pregnancy in a thousand. Because cancer during pregnancy is a rare event, most doctors have encountered few if any cases, and the medical literature offers few rigorous studies to provide guidance.
"It's extraordinarily difficult to do meaningful research in patients with cancer who are pregnant," said Dr. Clifford Hudis, chief of the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center, who estimates that in more than two decades of practice he has seen one pregnant patient with breast cancer "every year or 2."
In addition to the rarity of cancer in pregnancy, concerns about the risks of chemotherapy to the fetus pose a significant barrier to conducting clinical research in pregnant women with cancer, explained Dr. Ted Trimble, former head of gynecological cancer therapeutics with NCI's Cancer Therapy Evaluation Program.
"Most trial sponsors are not comfortable encouraging pregnant women to participate in a trial of any agent whose mechanism of action might cause birth defects or fetal death," Dr. Trimble said.
As more women delay childbearing until their 30s or 40s—ages at which cancer risk, while still low, begins to creep up—some researchers predict that cancer diagnoses during pregnancy will increase. Swedish researchers have estimated that the incidence of breast cancer diagnosed during pregnancy or within 2 years of delivery more than doubled between 1963 and 2002.
Toxic to DNA
Chemotherapy agents are known to cause malformations in laboratory animals. The risk of birth defects is highest during the first trimester of pregnancy when organs are forming.
"Chemotherapy agents are meant to interfere with rapidly dividing cells; they are supposed to be toxic to DNA," explained Dr. John J. Mulvihill, a specialist in cancer genetics at the University of Oklahoma Health Sciences Center.
Women and oncologists need to know it's possible to successfully treat cancer while continuing with a pregnancy.
—Dr. Elyce Cardonick
—Dr. Elyce Cardonick
Since 1984, Dr. Mulvihill has maintained the Registry of Pregnancies Exposed to Chemotherapeutic Agents, which has accumulated data from the medical literature since 1950 on the outcomes of 845 pregnancies in women treated for cancer. "It's not great population-based data," he said. "It's more a collection of rare clinical experience.
"We do see an excess of malformations, 19 percent, with first-trimester exposure to chemotherapy," Dr. Mulvihill continued. "Exposure in the second and third trimesters seems to have no increased adverse effects except when therapy is given very late in pregnancy, when it can cause transient effects like low white-blood-cell counts."
Given the obstacles to conducting clinical trials in pregnant women, studies based on data from registries—with all their limitations—provide the best evidence available about outcomes for children prenatally exposed to chemotherapy, according to Dr. Trimble.
Reason for Optimism
"After the first trimester, the concern is less about birth defects and more about potential for impaired organ or brain function, since the brain continues to develop throughout pregnancy, " said Dr. Elyce Cardonick, a maternal-fetal medicine specialist at Cooper University Hospital in Camden, NJ.
Dr. Cardonick maintains the Pregnancy & Cancer Registry, which since 1997 has compiled information on nearly 300 pregnancies in women with cancer, and is following 247 mothers and children over the long term. Findings from her studies and others offer some reason for optimism: In general, children prenatally exposed to chemotherapy do not appear to have higher rates of birth defects or developmental abnormalities than other children.
Mexican researchers closely followed 84 children whose mothers received chemotherapy for hematologic cancers during pregnancy, including 38 who were treated during the first trimester, for a median of 18 years. All the children were normal, physically and neurologically, and performed normally at school. Some gave birth to their own children, adding 12 second-generation offspring to the study cohort.
Premature birth is more likely than chemotherapy to impair the cognitive development of children prenatally exposed to chemotherapy, an international research group reported in September at a European oncology meeting. Of the 70 children they studied, who ranged in age from 18 months to 18 years, 47 were born prematurely. Although most of the children were normal, most of those with cognitive development problems were born early.
Lead researcher Dr. Frederic Amant, of University Hospitals Leuven in Belgium, said it was not clear whether chemotherapy caused the early deliveries, but in many cases preterm delivery was induced. "Our results suggest [inducement of early delivery] should be avoided," he said.
At the 2011 American Society of Clinical Oncology annual meeting, Dr. Jennifer Litton, a medical oncologist specializing in breast cancer at the University of Texas M. D. Anderson Cancer Center, reported on 41 children born to women who were treated during the second or third trimester with a standardized multidrug chemotherapy regimen in a prospective registry trial.
Overall, the children, now ages 1 to 21, are doing well, she said. Three to four percent have birth defects, equivalent to the national average for children not prenatally exposed to chemotherapy. The cohort has now increased in size to nearly 90 children, whom Dr. Litton and her colleagues are still following.
The M. D. Anderson study has enrolled 81 pregnant women with breast cancer since 1989 and has used the same chemotherapy regimen of 5-fluorouracil, doxorubicin, and cyclophosphamide since its inception. Pregnant patients are generally treated with older anticancer agents because of a lack of safety data for newer therapies, according to Dr. Trimble.
Don't Ignore a Lump
Data from the Pregnancy & Cancer Registry indicate that in about one in five cases doctors recommended terminating the pregnancy before starting cancer treatment, according to Dr. Cardonick. Anecdotally, she has heard of pregnant women who didn't tell their doctors about a lump or other abnormality because they feared they would be advised to terminate the pregnancy.
"Women and oncologists need to know it's possible to successfully treat cancer while continuing with a pregnancy," she said. "Women should not be afraid to bring a breast mass or mole to their doctor's attention.
"Most oncologists want to treat the patient as if she's not pregnant, and, for the most part, in the second and third trimester, they can," she continued. "But they need to make some adjustments. For example, you should not give chemo after the 34th week of pregnancy because, if the patient goes into labor while her white blood cell counts are low, the baby could be born with neutropenia."
Trina Pockett's doctor suggested she consider termination but supported her decision to continue with the pregnancy. She underwent four cycles of chemotherapy before her daughter, Kate, was born 6 weeks prematurely. After the birth she completed chemotherapy, followed by radiation treatment.
She has been cancer-free since 2001. Kate, who spent nearly 4 weeks in neonatal intensive care, is now a healthy 11-year-old who aspires to be a veterinarian. Pockett gave birth to a third child, Noah, in 2004.
In 2009, she achieved a personal goal when she competed in a half-marathon in San Diego. "To run in the same city where I had chemotherapy was very special," she said.
NCI Cancer Bulletin for November 29, 2011 - National Cancer Institute