Pregnancy and Cancer

Key Terms: Cesarean section, Colposcopy, Ectopic pregnancy, Hydatiform mole, Interdisciplinary team, Microcephaly, Molar pregnancy.

Definition

For the most part, cancer that strikes during a pregnancy is unrelated to the pregnancy. The exception is choriocarcinoma. This cancer is only found in pregnancy.

Description

Pregnancy can be a joyous time for a woman, but when cancer is diagnosed, a tremendous dilemma can arise, both for the woman and for her health care providers. Cancer is not common in pregnancy, and is rarely the cause of maternal mortality. However, in any pregnancy there are always two patients to consider—the mother and the fetus. When a pregnant woman has cancer, the health of the mother may be pitted against the well-being of the fetus. For women who do not have regular medical visits, pregnancy may be a time for regular prenatal visits. For them, screenings done in pregnancy may serve as an opportunity to detect a hidden cancer.

Interestingly, pregnancy also has some protective effects against breast cancer. Studies have firmly established that early full-time pregnancy helps lower risk for breast cancer for a woman's lifetime.

Choriocarcinoma arises from embryonic fetal tissue called the chorion and chorionic villi. It may be associated with a molar pregnancy, an ectopic pregnancy, and may even develop after the delivery of a normal fetus. It may be referred to as gestational trophoblastic disease (GTD), or gestational trophoblastic tumor. A non-malignant form is a hydatiform mole, but the tissue can become cancerous. Vaginal bleeding and high beta human chorionic gonadotropin (hCG) levels characterize the condition.

Ultrasound is effective in evaluating the mass to establish the presence or absence of a fetus and of a fetal heartbeat. The tissue must be evacuated and sent to pathology for evaluation. If cancerous cells are found, chemotherapy is begun. Chemotherapy has been shown to be extremely effective in treating choriocarcinoma. If left untreated, choriocarcinoma readily metastasizes, or spreads to other organs.

Incidence of GTD rises with maternal age. Women who desire future pregnancies should discuss this as part of the treatment plan to ensure fertility-sparing choices. Some women normally have high hCG levels. If they have some abnormal vaginal bleeding they can be incorrectly diagnosed as having choriocarcinoma if they have a high hCG level without other evidence of a pregnancy. Before undergoing chemotherapy or surgery, women should have a urine pregnancy test done as well, and/or have blood hCG tests done that are able to discriminate between various forms of hCG. Some laboratory hCG tests have a high false-positive rate, and are not designed to screen for hCG that is associated with cancer.

The most common cancers occurring during pregnancy, in descending order are:

• Cervical cancer. About 0.5 to 5.0% of cervical cancers occur in pregnant women, and about one-third of women are under 35 when given the diagnosis. Survival rates for pregnant versus non-pregnant women are similar. It is safe to have a Pap smear during a prenatal visit. Suspicious findings may lead to a colposcopy and biopsy. There may be increased bleeding from the biopsy site in the pregnant woman. If cervical cancer is found, the stage of cancer and trimester of pregnancy will determine if immediate surgery is needed or if treatment can be postponed until the fetus matures. With cervical cancer a cesarean delivery will be recommended, perhaps before full term of 40 weeks if the fetus' lungs are sufficiently mature.
• Breast cancer. Breast cancer occurs in about one out of every 3,000 pregnancies. As in non-pregnant women, infiltrating ductal carcinoma is the most prevalent type. When determining the type and stage, the tumor also will be evaluated for being estrogen receptor positive or negative (ER-positive, ER-negative). Pregnancy hormones accelerate the growth of ER-positive tumors. Pregnancy has less of an impact on ER-negative tumors. The pregnancy hormones can alter the test results and increase the number of false negatives of hormone receptor testing. Because of the normal breast changes in pregnancy, it is more difficult to detect a lump when pregnant, so diagnosis may be delayed while the tumor continues to grow. Pregnancy also increases the density of the breast and makes mammography less sensitive. Ultrasound can be used to differentiate between a fluid-filled lump and a solid tumor. About 67% of pregnant women with breast cancer have positive lymph nodes versus 38% of non-pregnant women. Studies indicate that about 47% of pregnant women with positive lymph nodes reach five-year survival versus 59% of non-pregnant women with positive nodes. For lactating women, some of the signs of mastitis are similar to the signs of inflammatory breast cancer. The diagnosis of cancer may be delayed because of the confusion. Some studies indicate that if an abscess is drained from a breast with mastitis, a sample should be sent to pathology. Pregnant women may experience bleeding from any procedures done on the breast due to increased vascularity.
• Melanoma. The average age for malignant melanoma is 45. About 30–40% of cases appear during the childbearing years. About 8% of women are pregnant at the time of diagnosis. During pregnancy the thickness of the lesion is greater, and nodal metastases more frequently occur. If there has been nodal metastasis, survival may be less than three years. Melanoma also can spread to the placenta and to the fetus. However, prognosis for the pregnant woman is greater if she carries to term (66.5% survival at five years), than if the pregnancy is terminated following diagnosis (33.5% survival at five years). Because most lesions appear on the extremities, treatment may begin during the pregnancy.
• Hodgkin's disease. Hodgkin's occurs about one in six thousand pregnancies. The average age for a diagnosis of Hodgkin's is 30. However, the prognosis for the pregnant woman is about the same as for a non-pregnant woman. Signs such as fever, night sweats, and unexplained weight loss indicate a higher stage of disease. A nodal biopsy can safely be done during pregnancy, but pregnancy can alter the test results. Treatment may include a short course of chemotherapy and radiation to the affected nodal area if the fetus can be adequately shielded. If this cannot be done safely, radiation may wait until after delivery. Nodal sclerosis is a common subtype of Hodgkin's and is frequently seen in adolescents and young adults. Non-Hodgkin's lymphoma is usually seen after the childbearing years.
• Ovarian cancer is extremely rare during pregnancy; only 1:10,000 to 1:100,000 full term deliveries are cases of this cancer. It is usually low grade and low stage (Stage 1) cancer. Germ cell malignancies are the most common form of ovarian cancer in young women. Germ cell cancer can grow very rapidly, so immediate chemotherapy will be discussed. During pregnancy alpha-fetoprotein levels are tested to check if the fetus may have a neural tube defect. However, this same test is used in the non-pregnant woman as a screening for germ cell cancer. Older women are more prone to epithelial and low malignancy potential ovarian cancers. It may be the prenatal ultrasound that first alerts a woman to her having ovarian cancer. The cancer tumor marker CA-125 is unreliable in pregnancy, as the levels go up during this time. Ovarian tumors may undergo torsion, or twisting, creating extreme pain that may be mistaken for appendicitis or an ectopic pregnancy if gestation is still early.
• Colorectal cancer is the third most common cancer in women, with 67,000 cases in 1999. About 10% of cases occur in patients under the age of 40; only about 2% of cases occur under the age of 30. Early occurrence is linked with high risk. There may be a delay in diagnosis, as some of the symptoms of colorectal cancer overlap symptoms seen in pregnancy. Because of the delay, a higher degree of disease may present at diagnosis. Women considering pregnancy should request screening prior to becoming pregnant. Signs of colorectal cancer include: nausea, abdominal bloating, backache, rectal bleeding, pain, and a change in bowel habits.
• Leukemia is quite rare during pregnancy, occurring in one out of 75,000 pregnancies. During pregnancy, acute myelocytic leukemia is usually the form seen. If treatment is begun right away, the prognosis for the pregnant woman is similar to that of the non-pregnant woman. Complete remission rates are also similar. Untreated, the disease can be rapidly fatal. The woman with leukemia is at greater risk for miscarriage, fetal growth retardation, prematurity and stillbirth.

Causes

As women delay their childbearing years into their forties and even fifties, an increase of cancer during pregnancy is occurring. This is due to the overlap of childbearing with the usual times of occurrence of certain cancers. The exact cause of most cancers is not yet known. However, estrogen is known to play a role in the development of endometrial and ovarian cancers. Research has shown that smoking increases the risk of developing cervical cancer, as well as other cancers.

Special Concerns

Decisions need to be made about commencing treatment, or delaying treatment until after the pregnancy is finished. Accurate staging of the tumor will be critical. The woman will be asked if the pregnancy is desired. If not, and if the gestation is less than 24 weeks, therapeutic abortion may be considered. Depending on the type and stage of the cancer, a delay in treatment might not affect the mother's prognosis. Fetal lung maturity may be monitored, so that a safe early delivery can be planned. As the fetus nears term, there is a significant decrease in morbidity and mortality for every extra two weeks it remains in utero.

A pregnant woman with cancer has a great need for an interdisciplinary team of experienced practitioners. Oncologists who have experience with treatment during pregnancy may be able to offer more choices for treating the cancer while maintaining a viable pregnancy. Practitioners also need experience in managing the treatment side effects in a safe way for the fetus. For example, corticosteroid use can increase the incidence of cleft palate, and affect maternal glucose intolerance.

Pregnant women should not take any over-the-counter medication, including herbal supplements, without first consulting their obstetrical provider. Medications and supplements considered safe for a non-pregnant woman may have harmful effects on the fetus.

Treatments

Cancer treatment usually involves some combination of surgery, radiation and chemotherapy. During the first trimester, or the first 12 weeks of gestation, the fetus' organs are developing and are very susceptible to teratogenic substances (substances that affect normal fetal development). When treatment is undertaken, it is most commonly in the second trimester, when early fetal development has already taken place.

When contemplating surgery during pregnancy, the risks for both mother and fetus must be considered. Abdominal surgery poses the greatest risk to the pregnancy, however some women can successfully have an ovary removed and still bring a healthy fetus to term. The removal of the ovary needs to take place after the first trimester, once the placenta has taken over the progesterone hormone production of the corpus luteum. General anesthesia is often chosen for surgery. The safest time for surgery is during the second trimester, but the risk of preterm labor, intrauterine growth retardation, and fetal death still exists. Mastectomy is often recommended for the treatment of breast cancer during pregnancy, although breast-conserving surgery may also be an option.

In the first 10 days following conception, radiation may kill the fetus, or may have no effect at all. From 10 days to 14 weeks, a fetus exposed to radiation is at risk for:

• intrauterine growth retardation
• central nervous system (CNS) abnormalities
• microcephaly
• severe mental retardation
• eye anomalies

From eight weeks until term, the fetus is still at risk for CNS abnormalities and milder forms of microcephaly and mental retardation from radiation. If the mother receives high doses of radiation, intrauterine death may occur. Because of the scarcity of research data, the threshold dose is unknown. Childhood cancers, other cancers later in life, and cancer appearing in later generations are also of concern. Research evaluating the outcome of the children of pregnant women exposed to the atomic bomb in Japan indicates the effects of radiation exposure may show up even five generations later.

When deciding on chemotherapy during pregnancy, several factors are considered:

• which chemotherapy drugs are effective for the woman's particular type of cancer, and of these which are safe for the developing fetus
• the stage of fetal development
• how long the chemotherapy will be administered
• how often it will be administered
• whether the chemotherapeutic agent crosses the placental barrier to the fetus

There are also maternal factors to consider. During pregnancy a woman's blood volume and cardiac output increase, which affects the drugs' concentration levels. If the woman has hyponatremia, this increases the drug concentration in her system. Maternal obesity can affect lipid-soluble drugs. As with radiation, the fetus is most susceptible during the first trimester. Congenital malformations and miscarriage are the most common consequences.

Questions to Ask the Doctor

• What type and stage is my cancer?
• If I were not pregnant how would you treat it?
• Since I am pregnant, how do you suggest treating it?
• What is the expected effect on my baby from the treatment?
• What is my prognosis?
• What part of the treatment can safely wait until after I deliver?
• What side effects can I expect from the treatment?
• What are the risks to me from this treatment?
• How will these treatments be managed?
• What long-term effects will my treatment have on my child?
• What alternative treatments are available to help me?
• Which members of my team are experienced in cancer and pregnancy?

Fortunately, some chemotherapy drugs seem to be well tolerated by the fetus during the second and third trimesters. These drugs include fluorouracil, doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine, and cyclophosphamide. Even so, the fetus is at risk for low birthweight, miscarriage, and premature birth. Chemotherapy is rarely administered near term. Treatment at this point may be delayed until after delivery, and during this time period the placenta is less able to effectively excrete the drug(s). Drugs that may not harm the fetus in utero may be harmful if consumed via the breast milk. For this reason, breastfeeding is usually discouraged. Methotrexate is known to be teratogenic and so is not given in pregnancy. Daunorubicin and cytarabine are teratogenic in the first trimester. There is not enough known about paclitaxel and pregnancy to consider its use. Of additional concern for the pregnant woman receiving treatment for cancer is the effects on the fetus of any medications that may be used to deal with treatment side effects.

Alternative and Complementary Therapies

A pregnant woman has many limitations on taking medications during pregnancy in order to protect the fetus. Medication that would ordinarily be available to deal with the side effects of cancer treatment may be harmful to the fetus. A helpful resource on the patient's interdisciplinary team is a practitioner with experience in the safe use of complementary therapies for cancer during pregnancy. Mind/body techniques such as guided imagery and meditation can help decrease some of the stress of this time. Acupuncture has been shown to be effective in dealing with the nausea associated with chemotherapy. Support groups can also be a great source of strength and information.

Resources

Books

Runowicz, Carolyn D., Jeanne A. Petrek, and Ted S. Gansler. American Cancer Society: Women and Cancer. New York: Villard Books/Random House, 1999.

Teeley, Peter, and Philip Bashe. The Complete Cancer Survival Guide. New York: Doubleday, 2000.

Periodicals

"Pregnancy Has a Protective Effect Against Breast Cancer." Medical Devices & Surgical Technology Week March 28, 2004: 40.

Rotmensch, S., and L. Cole. "False Diagnosis and Needless Therapy of Presumed Malignant Disease in Women With False-positive Human Chorionic Gonadotropin Concentrations." Lancet February 26, 2000: 712–5.

Organizations

The American Cancer Society. (800) ACS-2345. .

Cancer Research Institute. 681 Fifth Ave., New York, NY 10022. (800) 992-2623. .

The Gilda Radner Familial Ovarian Cancer Registry. Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263-0001. (800) 682-7426. .

National Cancer Institute. Building 31, Room 10A31, 31 Center Dr., MSC 2580, Bethesda, MD 20892-2580. (301) 435-3848. .

National Cancer Institute Cancer Trials Web Site. . .

National Center for Complementary and Alternative Medicine. NCCAM Clearinghouse, PO Box 8218, Silver Spring, MD 20907-8218. (888) 644-6226. .

Oncolink at the University of Pennsylvania. .

Women's Cancer Network. c/o Gynecologic Cancer Foundation, 401 N. Michigan Ave., Chicago, IL 60611. (312) 644-6610. .

—Esther Csapo Rastegari, R.N., B.S.N., Ed.M.; Teresa G. Odle