Cancer diagnosis during pregnancy is rare.1 This incidence is expected to increase, however, as increasingly older women are becoming pregnant, and the frequency of some cancers is rising in younger populations.2,3 The most common types of cancers diagnosed during pregnancy or during the initial postpartum period are breast cancer, thyroid cancer, melanoma, hematologic cancers such as leukemia or lymphoma, and cervical or uterine cancer.4
The management of pregnant patients with cancer is challenging for clinicians and patients because of the consideration of both the needs of the mother and potential harms to the fetus.2,3 Data for the treatment of cancer during pregnancy are limited to retrospective or observational cohorts, case series and reports, and expert experience.5
Cancer Diagnosis and Treatment During Pregnancy
The diagnosis of cancer during pregnancy may be delayed because symptoms of many cancer types may mimic normal symptoms of pregnancy.3,5 This may result in a more advanced cancer at diagnosis. The definitive diagnosis of cancer is important during pregnancy and should not be delayed. Most diagnostic techniques can be safely conducted during pregnancy, including ultrasounds, biopsy, and magnetic resonance imaging (MRI); however, MRI with contrast is typically avoided due to potential effects of gadolinium-based contrast agents.2,5 Mammography can also be safely conducted, as modern shielding techniques greatly limit the amount of radiation that reaches the fetus.2
Cancer treatment during pregnancy requires a multidisciplinary approach that includes not only the oncologic team, but also the obstetrics team, including maternal-fetal medicine.2,6 The decision to initiate treatment will depend on the type and stage of cancer, the gestational age, and the treatment options, as well as the desires of the patient.2 In addition, treatment should be planned with a goal of achieving a full-term pregnancy in mind.5 Surgery is generally safe, and recommendations are similar to those of women who are not pregnant.2
Treatment should be avoided during the first trimester because that is when the fetus is undergoing organogenesis and the greatest risk of fetal harm is present. For more aggressive cancer types diagnosed during the first trimester, termination may be recommended so that intensive therapy can be initiated.5 Most studies suggest that treatment with chemotherapy is generally acceptable during the second and third trimesters, and should be administered using established dosing.2,3,5
Studies have shown that anthracycline-based regimens for breast cancer, such as 5-fluorouracil, doxorubicin, and cyclophosphamide; and platinum agents such as cisplatin for cervical cancer; can be used with generally favorable maternal and fetal outcomes.2,6 Case reports suggest that treatment of colorectal cancer during pregnancy with leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) is acceptable, but anti-EGFR therapies should be avoided.3 For hematologic malignancies, the typical standard of care for Hodgkin lymphoma, which is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), can be administered.5 Treatment of non-Hodgkin lymphomas is more challenging, given there are numerous subtypes. Although many chemotherapy regimens can be used in the second and third trimesters, other agents, such as rituximab and tyrosine kinase inhibitors (TKIs), should be avoided due to high risks of fetal harm.
There are no studies that examine the effects of treatment with immune checkpoint inhibitors during pregnancy, with the exception of a single case report.7 Theoretically, checkpoint inhibition should be avoided because checkpoint pathways are important for providing immune tolerance to the fetus, and inhibition of checkpoint pathways is associated with an increased risk of miscarriage.
In the case study, a woman presented with a relapse of melanoma that was metastatic and harbored a BRAF V600E mutation. Because TKI therapy is contraindicated, the team decided to initiate nivolumab plus ipilimumab using approved dosing. The woman experienced a partial response, and the infant was delivered by cesarean at 32 weeks due to placental abnormalities and a low basal heart rate. As of 11 months of age, the child has shown no negative effects due to this treatment exposure, and the woman continued to experience a response, despite early discontinuation of therapy due to immune-related hepatitis.
Radiotherapy is contraindicated in pregnancy due to the risk of fetal harm; although, for some cancer types, radiation may be required.2,5