Management of Pregnant Patients With Cancer

May 15, 2016

Approximately 1 in 1,000 pregnancies are complicated by a cancer diagnosis, and there is speculation that the incidence of cancer during pregnancy will increase as more women delay childbearing. The cancers that most commonly afflict pregnant women include breast and cervical cancer, as well as melanoma, lymphoma, and acute leukemia.

Introduction

Approximately 1 in 1,000 pregnancies are complicated by a cancer diagnosis,[1] and there is speculation that the incidence of cancer during pregnancy will increase as more women delay childbearing. The cancers that most commonly afflict pregnant women include breast and cervical cancer,[1-5] as well as melanoma, lymphoma, and acute leukemia. The diagnosis of cancer during pregnancy poses a dilemma for the mother-to-be and her family, as well as her obstetrician and the treating oncologist. In the past, it was universally assumed that the pregnancy had to be either terminated or cancer treatment delayed until after the birth of the child. This often led to poor outcomes, since delaying treatment resulted in more advanced disease. However, many women now want to continue their pregnancies, and therefore the impact of treatment on the patient and the unborn baby must be considered. Significant evidence has shown that cancer treatment can proceed without harm to the developing fetus or compromise to the long-term survival of the mother. Studies have shown no developmental differences in children exposed to chemotherapy in utero compared with their non-exposed peers.[6,7] In light of these findings, it is important to have practice guidelines for treating pregnant cancer patients.

How Is a Pregnant Woman Different?

Pregnancy brings with it many anatomic and physiologic changes, including increased hormone production and circulation. Maternal blood volume increases, as does cardiac output and heart and respiratory rate.[8] Blood pressure is often initially lower, but may increase later in pregnancy and may pose a danger to the pregnant woman and the unborn baby. Anatomically, the gravid uterus will displace abdominal organs upward, and gastric emptying and rates of digestion will be altered. All of these changes need to be recognized and taken into consideration when caring for and devising a cancer treatment plan for a pregnant woman.

Initial Assessment of a Pregnant Woman With Cancer

Treatment plans will depend not only on the type and stage of cancer, but on the gestational age of the unborn baby. Therefore, it is important to determine the gestational age by gathering information such as the patient’s last menstrual period, and if necessary, ordering an ultrasound to aid in dating the pregnancy. Once gestational age is determined, staging and workup of the disease may have to be modified.

Radiographic studies such as computed tomography (CT) or positron emission tomography (PET) scans may be contraindicated because of the high level of radiation exposure to the developing fetus. Alternate methods of staging, such as magnetic resonance imaging (MRI) without contrast or ultrasound, will need to be considered. Although gadolinium has not been reported to cause any adverse effects on developing fetuses, it is still contraindicated in pregnancy. If x-rays are necessary, the abdomen should be shielded. Bone scans and nucleotide scans are also contraindicated because of the high level of radiation exposure.[4,5,8-16]

Once the extent and type of cancer is determined and a treatment plan proposed, the patient should be counseled by a maternal-fetal specialist in addition to an oncologist. Treatment may have implications for the development of the fetus and for the timing of delivery. Some aggressive types of cancers, such as acute leukemias, have a poor prognosis for the developing fetus, especially if diagnosed in the first trimester. Complications due to pancytopenia include infections, including endometritis and chorioamnionitis, which may be life-threatening to the mother, and which often lead to miscarriage. Therefore, in these situations, termination of the pregnancy may need to be discussed.

If radiation therapy is the treatment of choice for a given cancer, such as with cervical or vulvar cancer, then the physician and the patient should decide whether to move forward with chemotherapy only, or interrupt the pregnancy. Radiation treatment during pregnancy is usually not administered because of the amount of internal scatter of radiation. This can lead to serious fetal malformations and other consequences, such as leukemia. Some cancers, such as melanoma, carry an increased risk for placental and fetal metastases, and thus the placenta should be examined after birth and the patient counseled accordingly.

Surgery During Pregnancy

Surgery for cancer is ideally planned during the second trimester of pregnancy. Although evidence that anesthetic agents can cause miscarriage is very limited and appears to be mostly relevant to repeated exposure, it is still advisable to wait until the pregnancy is well-established but previable.[2-4]

About 20% of known pregnancies end in spontaneous abortion; thus, efforts should be made to minimize the fetus’ exposure to potential harm. Additionally, none of the anesthetic agents are considered safe during pregnancy, so the recommendation is to wait until organ formation in the fetus is completed, usually after the first trimester. Surgery in the third trimester should be avoided if at all possible, since there is a possibility of premature labor and delivery.[12]

Special consideration for surgical procedures include placing the patient in left lateral decubitus position, if possible, to minimize compression of the inferior vena cava by the gravid uterus. Preoperative and postoperative fetal heart tones should be documented to ascertain fetal wellbeing. Intraoperative fetal monitoring is rarely indicated, since many temporary variations in fetal heart rate will resolve spontaneously. Intrauterine resuscitation is usually preferable to emergent delivery. It is important to keep the maternal blood pressure and heart rate controlled.[11,15]

Pain control intraoperatively and postoperatively can be achieved with narcotic pain medications. Although many patients voice concern about causing narcotic addiction in the fetus, this is rarely an issue if pain medication is taken only for pain control.

Certain antibiotics need to be avoided, namely all quinolones and tetracyclines. Quinolones interfere with development of the bony skeleton, and tetracyclines lead to abnormal tooth development. If surgery in the third trimester cannot be avoided, then it should be performed at a hospital with a tertiary Neonatial Intensive Care Unit and appropriate neonatal support personnel. Many surgical procedures can be performed under local blocks with minimal sedation, thus minimizing exposure to anesthetic agents.[16]

Abdominal surgery should generally be avoided or limited, since irritation of the gravid uterus can lead to miscarriage or preterm labor. Guidance should be sought from Maternal Fetal Medicine on how to opitimize tocolysis during and after surgery, if abdominal surgery is absolutely necessary. Laparoscopy is possible until about 15 to 16 weeks gestation, but later in the pregnancy it becomes more difficult, since the size of the gravid uterus will interfere with trochar placement and visualization of the intra-abdominal organs.[2-4,7,17,18]

Care During Cancer Treatment

As previously mentioned, studies have been conducted that did not demonstrate an increased risk of birth defects from chemotherapy exposure during pregnancy.[6,7] Additionally, it seems that any learning disabilities or other developmental delays experienced by children exposed to chemotherapy in utero are a result of prematurity rather than chemotherapy exposure. However, there is still the risk of intrauterine growth restriction from exposure to chemotherapy, or possibly from the resulting cytopenias in the mother.[13,16] Although most chemotherapeutic agents cross the placenta, it seems that the quantity is not large enough to have a significant effect on the developing fetus. In addition to intrauterine growth restriction, the risks associated with chemotherapy during pregnancy include preterm labor and birth, oligohydramnios, and polyhydramnios. Underlying medical comorbidities of the mother, such as hypertension, diabetes, or gestational diabetes, can also place the fetus at risk. Therefore, growth scans and assessment of amniotic fluid and fetal well-being should occur on a regular basis, at least prior to each cycle of chemotherapy.[6,7,18-21]

Visits with the maternal-fetal specialist should detect problems with maternal or fetal health unrelated to cancer or cancer treatment, but which may nonetheless have an impact on further treatment decisions. Potential problems unrelated to cancer diagnosis include gestational diabetes, preterm labor, preeclampsia, and toxemia.

Furthermore, the maternal-fetal specialist can counsel the patient and her family on possible outcomes in the immediate postpartum and neonatal period. For example, some chemotherapeutic agents have been associated with neonatal anemia, leukopenia, and thrombocytopenia, as well as transient or permanent elevation of creatinine. Carefully weighing the risks and the benefits to both the mother and the fetus may, in some cases, lead to delaying treatment until the postpartum period, especially in patients who are close to term. These decisions should be made by all parties involved-the patient and her family, the oncologist, and the maternal-fetal specialist; if necessary, a neonatologist may be helpful if early delivery is considered. Delivery should be carefully timed so as not to occur during the nadir in blood counts after chemotherapy, as this can lead to serious maternal complications and an increased risk of neonatal complications, such as neonatal sepsis.[22-24]

Conclusion

Because cancer during pregnancy is rare and can result in unexpected events, care of the pregnant patient should involve a multidisciplinary team who are in close communication. The treating oncologist, while the expert in cancer treatment, may need to defer to and closely collaborate with the maternal-fetal specialist.

At our institution, we have devised an algorithm and a specialized care team with the aim of optimizing collaboration and communication. Since we are a cancer treatment center, we are not able to provide obstetric or neonatal care; thus, all of our pregnant patients receive their obstetric care from an outside group of maternal-fetal specialists. At our center, we have cared for many pregnant women who have had successful pregnancies without interrupting their cancer treatment. Although many women desire to continue their pregnancy, we should not judge those who, for various reasons, may choose to terminate. Each case is different, and some cancers may have worse outcomes if they occur during pregnancy. We can and should support the woman and her family in the path they wish to take.

Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Chervenak FA, McCullough LB, Knapp RC, et al. A clinically comprehensive ethical framework for offering and recommending cancer treatment before and during pregnancy. Cancer. 2004;100:215-22.

2. Moran BJ, Yano H, Al Zahir N, et al. Conflicting priorities in surgical intervention for cancer in pregnancy. Lancet Oncol. 2007;8:536-44.

3. Jacobs IA, Chang CK, Salti GI. Coexistence of pregnancy and cancer. Am Surg. 2004;70:1025-9.

4. Weisz B, Meirow D, Schiff E, et al. Impact and treatment of cancer during pregnancy. Expert Rev Anticancer Ther. 2004;4:889-902.

5. Pavlidis NA. Coexistence of pregnancy and malignancy. Oncologist. 2007;7:279-87.

6. Amant F, Vandenbroucke T, Verheecke M, et al. Pediatric outcome after maternal cancer diagnosed during pregnancy. N Engl J Med. 2015;373:1824-34.

7. Cardonick EH, Gringlas MB, Hunter K, Greenspan J. Development of children born to mothers with cancer during pregnancy: comparing in utero chemotherapy-exposed children with nonexposed controls. Am J Obstet Gynecol. 2015;212:658.e1-8.

8. Torgersen KL, Curran CA. A systematic approach to the physiologic adaptations of pregnancy. Crit Care Nurs Q. 2006;29:2-19.

9. Theriault R, Hahn K. Management of breast cancer in pregnancy. Curr Oncol Rep. 2007;9:17-21.

10. Rimes S, Gano J, Hahn K, et al. Caring for pregnant patients with breast cancer. Oncol Nurs Forum. 2006;33:1065-9.

11. Shaver SM, Shaver DC. Perioperative assessment of the obstetric patient undergoing abdominal surgery. J Perianesth Nurs. 2005;20:160-6.

12. Ní Mhuireachtaigh R, O’Gorman DA. Anesthesia in pregnant patients for nonobstetric surgery. J Clin Anesth. 2006;18:60-6.

13. Loibl S, von Minckwitz G, Gwyn K, et al. Breast carcinoma during pregnancy. International recommendations from an expert meeting. Cancer. 2006;106:237-46.

14. Woo JC, Yu T, Hurd TC. Breast cancer in pregnancy: a literature review. Arch Surg. 2003;138:91-8; discussion 99.

15. Challoner K, Incerpi M. Nontraumatic abdominal surgical emergencies in the pregnant patient. Emerg Med Clin North Am. 2003;21:971-85.

16. Williams SF, Schilsky RL. Antineoplastic drugs administered during pregnancy. Semin Oncol. 2000;27:618-22.

17. Gemignani ML, Petrek JA. Pregnancy-associated breast cancer: Diagnosis and treatment. Breast J. 2000;6:68-73.

18. Kuczkowski KM. Nonobstetric surgery in the parturient: anesthetic considerations. J Clin Anesth. 2006;18:5-7.

19. Peters BG, Bray JJ, Masidonski P, et al. Issues surrounding adjuvant chemotherapy for breast cancer during pregnancy. Oncol Nurs Forum. 2001;28:639-42.

20. Gwyn K. Children exposed to chemotherapy in utero. J Natl Cancer Inst Monogr. 2005;34:69-71.

21. Leslie KK, Koil C, Rayburn WF. Chemotherapeutic drugs in pregnancy. Obstet Gynecol Clin North Am. 2005;32:627-40.

22. Hahn KM, Johnson PH, Gordon N, et al. Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero. Cancer. 2006;107:1219-26.

23. MacDougall MK, LeGrand SB, Walsh D. Symptom control in the pregnant cancer patient. Semin Oncol. 2000;27:704-11.

24. Berry DL, Theriault RL, Holmes FA, et al. Management of breast cancer during pregnancy using a standardized protocol. J Clin Oncol. 1999;17:855-61.