Approximately 140 in 100,000 pregnant women receive a cancer diagnosis. Of these diagnoses, 0.1% are considered malignant tumors.
I recently cared for a Hispanic patient, age 42 years, who presented to the emergency department with fatigue, bruising, and low-grade fever. After a complete blood count was drawn, it was revealed that she had a white blood cell count of 75,000/μl and hemoglobin level of 6.0 g/dL, as well as a platelet count of 23,000×103/μL. She was admitted to the hematology floor for further diagnostic analysis.
Ultimately, a bone marrow biopsy revealed that she had acute lymphoblastic leukemia. Upon being informed that she would be admitted for approximately 4 weeks and would receive augmented Berlin-Frankfurt-Munster chemotherapy, this woman began to cry. She was 28 weeks pregnant and could not fathom what this outcome might mean for her baby girl.
On top of this, she worried about her husband. Would he be able to care for the baby if she still required cancer treatment after giving birth? She had no extended family to call on, and she was the primary source of income for their family.
Caring for this patient made me think about the many women who find themselves in this situation; approximately 140 in 100,000 pregnant women receive a cancer diagnosis.1 Of these diagnoses, 0.1% are considered malignant tumors.2 The most common forms of cancer seen among pregnant women are breast cancer, melanoma, cervical cancer lymphoma, and leukemia.2 Women over the age of 40 years are 4 times more likely to get cancer than women under the age of 30 years.3 Although the pathophysiology of cancer during pregnancy is still not fully understood, it has been known to be associated with suppression of the immune system, increased vascularization and permeability, as well as hormonal changes.2
Cancer cells develop from normal cells and are therefore widely recognized by the immune system. A healthy immune system consists of B lymphocytes and T lymphocytes that function to protect the body from foreign pathogens. When cancer cells escape attack by the immune system, this leads to “development, outgrowth, invasion, and metastatic activity.”1 Consequently, malignancies such as cancer lead to systemic inflammation, irreversible lymphopenia, anemia, fatigue, and depletion of protein.4
While the fetus is growing, the immune system is in a modulated state.1 This state is essential for maintaining the pregnancy and developing the maternal/ paternal antigens that protect the fetus. Specific hormones, enzymes, and cytokines are necessary for fetal protection.
Early diagnosis is vital to the successful treatment of cancer in pregnancy. Unfortunately, cancer can be difficult to diagnose in pregnant women because of ambiguous symptoms such as fatigue, abdominal pain, changes to the breast, nausea, vomiting, and anemia. This often leads to late presentation, complex treatment, and poor prognosis.
Physiological changes manifested in pregnancy lead to alterations among the body systems that reduce the efficiency of laboratory values. For example, hemoglobin and hematocrit reduction are normal changes seen among pregnant women. By contrast, elevation of alkaline phosphatase and lactate dehydrogenase (LDH) are also seen, and further validate potential delays in definitive diagnosis.5
Tumor markers are known to be useful in the diagnosis, follow-up, and treatment of patients with cancer, but in pregnant patients they often do not provide definitive sensitivity and specificity.2 Cancer antigen (CA) 15-3, squamous cell carcinoma antigen, CA 125, and α-fetoprotein levels should be avoided for definitive diagnostic work-up.
In contrast, carcinoembryonic antigen, CA 19-9, LDH, anti-Mullerian hormone, and human epididymis protein 4 levels can be used given their absence of elevation in pregnancy.6
Diagnostic exams such as radiological studies, CT, and MRI should be individualized for the treatment of pregnant women with cancer. High doses of irradiation above 100 mGy may cause significant impairment to the fetus and should be avoided. If abdominal shielding can be utilized, CT and fluoroscopic imaging can be performed. Contrast that includes gadolinium is not recommended because it crosses the placenta, leading to teratogenic effects on the fetus.2 Iodinating contrast, however, has not been shown to have a detrimental impact on the fetus when used in animal studies; however, it should be avoided.2
In conclusion, chemotherapy is known to have low molecular weight and can have teratogenic effects on the fetus. During the first 2 weeks after conception, chemotherapy can lead to a miscarriage; however, an embryo does have the ability to survive given the rapid differentiation of hematopoietic stem cells.1 From 2 to 8 weeks, the development of organs occurs, and continued insult to the fetus can develop, leading to malformation.1 During the second and third trimesters, fetuses can also be at risk of low birth weight, preterm labor, and growth restriction.1 Despite the risks during these trimesters, standard guidelines should be executed without dose reduction. A risk-benefit ratio should always be considered per patient as well as allogeneity given its impact on immunotherapy agents.
The patient I cared for is currently going through standard chemotherapy without complications. She has delivered her baby, who is currently in the neonatal intensive care unit. The family is receiving psychosocial, spiritual, and financial support to help them cope.
As I began to further research this topic, I quickly realized there is still a wide gap in evidence-based research regarding optimal care for this patient population. Going forward, I urge the oncology community to commit to putting resources behind these women and finding ways to improve our care delivery for women like my patient and their babies.
References