By Elizabeth Whittington

After six months of trying to have a baby, Amanda Olivere, a middle school teacher in Newark, Delaware, and her husband were joyfully surprised to find out she was pregnant. When the doctor’s office called a couple of days later, she feared the worst—an impending miscarriage. What Olivere didn’t expect to hear was that her routine blood work revealed she had chronic myelogenous leukemia (CML), a slow-growing cancer of the blood caused by the overproduction of white blood cells.

Researchers estimate that as many as one in every 1,000 pregnancies occurs in women with cancer. Very few studies exist to guide women and their doctors with this unique issue, especially when new treatments bring more unknowns. Many women in the past have been advised to terminate the pregnancy because of possible birth defects from therapy or a higher risk of dying from the disease, but as more data are compiled, these beliefs are being challenged and women are being given more options.

For Olivere, she had to decide whether to terminate her pregnancy or postpone taking a new life-saving drug, Gleevec® (imatinib), which has very limited data on whether it caused birth defects. Despite knowing the risks of delaying treatment, Olivere decided to wait until she was further along in the pregnancy before taking Gleevec. Unfortunately, five weeks later, Olivere miscarried.

“The baby was our miracle,” says Olivere, who wonders how long it would have taken her to be diagnosed if not for the pregnancy. “If the baby had survived, we would have called him or her Gabriel or Gabriella because that means ‘messenger’.”

Olivere started Gleevec after her miscarriage and within weeks her white blood cell count was under control. Olivere and her husband were eager to try again for another baby, but they were worried about the effect Olivere’s cancer and Gleevec would have on her and another pregnancy. Her doctor made her a deal: Stay on the medicine, reach the highest level of remission and then they’ll talk about babies. When Olivere reached a point where the mutant chromosome that causes CML was no longer detectable in her blood over several months, doctors finally gave her the go ahead to try for another baby. Two weeks later, she was pregnant.

Armed with information about her options, Olivere quit taking Gleevec during her second pregnancy. She is monitored biweekly and knows the leukemia could return and mutate, making Gleevec less effective. She has reached her goal of making it to the second trimester without Gleevec, and, depending on her leukemic levels, hopes to remain off the drug until the birth.

Chemotherapy May Be Safe

In the past, physicians often advised pregnant women with cancer to terminate or induce early delivery, depending on how far the pregnancy had progressed, so patients could undergo treatment immediately. Fueled by the false belief that pregnancy worsened the cancer prognosis, coupled with the unknown risk for birth defects, some doctors refused to treat pregnant women, forcing them to make a difficult decision.

Although the incidence is rare, researchers are now beginning to gather enough data to show that cancer drugs in general pose less risk than once believed and treatment may be delayed in certain cancers until the fetus is more mature. John Mulvihill, MD, professor of genetics in the pediatric department at the University of Oklahoma, has compiled more than 700 cases of fetal exposure to cancer treatment in the past 20 years through literature reviews and talking with doctors and patients. While Dr. Mulvihill admits the data are imperfectly gathered, “they are the only data available to shed some light on a very traumatic situation,” he says.

Other programs have compiled similar data, greatly increasing knowledge on the effects of different chemotherapies on the fetus at various gestational ages. Cytoxan® (cyclophosphamide) and 5-fluorouracil (5-FU) have been shown to cause birth defects when given in the first trimester, but are considered safe after that time. Nolvadex® (tamoxifen), given for five years to women after estrogen receptor-positive breast cancer therapy, increases the risk of birth defects. Methotrexate induces miscarriage by preventing embryonic cells from dividing and multiplying. Neither tamoxifen nor methotrexate is recommended at any stage during pregnancy. Because of the lack of data on the safety of Herceptin® (trastuzumab) and taxanes, such as Taxol® (paclitaxel) and Taxotere® (docetaxel), they are also not typically given during pregnancy.
The placenta, which acts as a barrier to harmful agents, partially protects the fetus from the cancer and many chemotherapies, although there have been a handful of cases in which cancer was transferred to the fetus in late-stage disease. Studies have shown fetuses exposed to general chemotherapy during the first trimester have a 19 percent risk for birth defects because the fetus is growing rapidly and forming organs, a process called organogenesis. During the second and third trimester, the risk drops to 5.5 percent. The risk for birth defects in the general population is between 3 and 5 percent.

“It’s very dramatic and poignant and unfortunate that we have to choose between two lives,” Dr. Mulvihill says. “The notion that there is an 80 percent chance the baby will be normal [if chemotherapy is taken during the first trimester] is quite reassuring to some women.” Nevertheless, experts say the nearly 20 percent risk of birth defect is cause for great concern.

A small number of retrospective studies suggest exposure to chemotherapy in utero during the second and third trimester does not increase the risk of long-term mental or neurological abnormalities or infertility for the child. However, doctors caution that data detailing issues of chemotherapy and pregnancy are limited.

Breast Cancer and Pregnancy

Breast cancer is by far the most common cancer diagnosed during pregnancy, occurring in nearly one of every 3,000 pregnancies. Although it was initially believed that pregnant breast cancer patients did not fare as well as nonpregnant patients, it is now believed that there is no difference in survival when comparing pregnant with nonpregnant patients with the same stage of breast cancer. Pregnant breast cancer patients are often diagnosed with later-stage disease because of delays in diagnosis and the aggressiveness of breast cancers often seen in younger women. In addition to breast cancer, lymphoma, leukemia, melanoma and cervical cancer are also more commonly seen in pregnant women because these cancers are more likely to strike young women.

After her grandmother and mother died of breast cancer at a young age, Gina Yarbrough of Dallas feared she too would be diagnosed with the disease. Within six weeks of a physical exam by her doctor in 1997, she noticed a lump in her breast during the 16th week of pregnancy. Because her disease was so aggressive, all three of Yarbrough’s doctors—her obstetrician, surgeon and oncologist—recommended she not continue the pregnancy.

“I think my husband was worried that I wouldn’t be able to go through with it and he would end up losing me for sure,” says Yarbrough. When they returned home from the consultation, her 3-year-old daughter met her at the door. “It wasn’t until I saw her that I considered going through what the doctors had suggested. It came to me what I needed to do because I wanted to see her grow up.”

Yarbrough has since met many women who share her experience. While many women in the past few years have continued their pregnancy during treatment, Yarbrough says that at the time of her pregnancy, there was a lack of options and little information on the subject. “No doctor could say what would happen to me if I remained pregnant.” Although Yarbrough’s treatment didn’t affect her fertility, she feared recurrence with another pregnancy. After looking into adoption, she and her husband had a surrogate carry their second child.
In the eight years since Yarbrough’s diagnosis, researchers have learned that most pregnant women with breast cancer can successfully follow the same management as non-pregnant young women, including surgery and treatment with agents such as Adriamycin® (doxorubicin), 5-FU and Cytoxan. These agents are crucial for many patients, pointing to a need for guidelines.

Deciding on Treatment

Because there is such limited information and most of it only in the past five to 10 years, many doctors are unaware of the recent studies on the subject, says Karin Gwyn, MD, a breast oncologist at Houston’s M.D. Anderson Cancer Center who specializes in breast cancer during pregnancy.

“Getting the word out is the best thing we can do, including educating our physician population and our patient population,” Dr. Gwyn says, including what is considered safe for the mother and the fetus, such as new treatments and diagnostic procedures. “People seem to think that you have to wait until after delivery to do a mammogram or a biopsy, and that’s not the case. It’s amazing the number of women that have come to me who have already had mastectomies and surgeries without ever having a mammogram.”

The amount of radiation exposure to a fetus from a mammogram is minimal, and a lead shield covering the abdomen offers additional protection. Magnetic resonance imaging (MRI) is also safe, but if the patient is being scanned for breast cancer, she must lie on her stomach during the procedure, which can limit its use in pregnant patients. Ultrasound is also commonly used.

While diagnostic levels of radiation can be given in relatively safe amounts, radiation therapy is not recommended because of the potential negative effects on the fetus, including birth defects. For this reason, chemotherapy and non-gynecological surgery are the two forms of therapy recommended for pregnant cancer patients.

In the general population, a small percentage (0.5 to 2 percent) of pregnant women undergo surgery unrelated to their pregnancy. The risk of low birth weight and minor birth defects is slightly higher when general anesthesia is used in the first two trimesters.

Several studies have shown that termination of a pregnancy does not increase survival, but based on the age of the fetus, the cancer’s stage and the optimal treatment regimen, doctors may still advise termination of the pregnancy. In cervical cancer, for example, termination or early delivery of the fetus is recommended by most doctors because hysterectomy and radiation therapy are the standard treatment, except in early-stage disease.

In pregnant women with metastatic cancer, the ability to carry the fetus to term and the potential impact of therapy upon the health and well-being of the fetus should be considered, but Dr. Gwyn and her colleague, Richard Theriault, DO, have treated women with metastatic breast cancer who have given birth to healthy babies.

“It’s really more where the disease is, how much of it there is and what drugs you have to use,” says Dr. Gwyn, who notes the decision is ultimately left to the woman and her support team.

As more doctors learn about additional treatment options for this small population, more questions will be answered regarding the effects of different cancers and therapies on the mother and the fetus, giving the patient more choices involving her treatment and pregnancy.

As for Olivere, she and her husband Michael want just one more surprise after the highs and lows of learning about her pregnancy and cancer diagnosis—they have decided not to find out the sex of the baby. “I get an ultrasound every month, so it’s going to be hard,” she says, “but we want a good surprise.”