Cancer in pregnancy

Published on 09/04/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 1271 times

19 Cancer in pregnancy

Cancer during pregnancy poses a very challenging situation. Cancer complicates 0.02–0.1% of pregnancies. The oncologist faces the difficult situation of optimizing the care of the mother without causing harm to the foetus. The common tumours diagnosed during pregnancy are malignant melanoma, breast cancer and cervical cancer.

Diagnostic work-up

All patients require a complete physical examination. Although histological diagnosis with fine needle aspiration cytology and core biopsies are safe, general anaesthesia during the first trimester carries a 1–2% risk of spontaneous abortion. Endoscopic biopsies as well as lumbar puncture and bone marrow examinations are safe. Radiological investigations should be restricted to minimize the foetal exposure to ionizing radiation. A foetal exposure dose of 1 mGy is considered safe. Box 19.1 shows various imaging procedures and uterine/foetal exposure dose. A dose of less than 100 mGy (10 cGy) is associated with less than 1% risk of foetal malformation and carcinogenesis and hence, in the event of inadvertent exposure of pregnant women to radiation, termination of pregnancy is not recommended if the foetal dose does not exceed this limit.

Box 19.1
Uterine/foetal radiation dose during various radiological investigations

Investigation Uterine/foetal dose
Chest X-ray 0.000005 Gy
Abdominal X-ray 0.022 Gy
Mammogram 0.04 Gy
Chest CT scan 0.002 Gy
Abdominal CT scan 0.02 Gy
Pelvic CT 0.07 Gy
Barium enema 0.036 Gy
IVU 0.045 Gy
Bone scan 0.018–0.045 Gy

1 Gy = 100 cGy = 1000 mGy

During the first trimester of pregnancy, radiological investigations are indicated only if absolutely necessary. Chest X-ray with lead apron is considered safe and hence can be used with ultrasound sonogram for initial evaluation. MRI without gadolinium (which crosses the placenta) can be used to rule out metastatic disease in the brain, liver and bone when indicated. Avoidance of MRI in the first trimester of pregnancy has been suggested due to the risk of foetal heating/cavitation. Abdominal X-rays, CT scans and isotope scans should be avoided during pregnancy. However, a final decision to perform these investigations is based on the risk benefit for the mother (your patient), their expected survival and the gestation of the foetus.

Systemic treatment

Most cytotoxic drugs have a low molecular weight of less than 600 kDa and can cross the placenta. The concern is that these agents can cause various mutagenic, teratogenic and carcinogenic effects in the foetus. Physiological changes due to pregnancy such as change in haemodynamics and renal clearance will also alter the metabolism, distribution and elimination of cytotoxic agents leading to unpredictable effects. Chemotherapy interferes with organogenesis in the first trimester, leading to a high risk of teratogenesis (10% with single agent and 20% with combination) and hence is not advised. After the first trimester organogenesis is complete except for the brain and gonads. Chemotherapy during this period can cause foetal growth retardation (2-fold risk), stillbirths (5%), premature delivery (5%), low birth weight (7%) and myelosuppression (4%). However, the risk of teratogenesis is almost similar to the general population (2–3%); but there is concern about risk of sterility, defects in intellectual function and other organ dysfunction due to in utero exposure of chemotherapy.

Alkylators and anti-metabolites are the most teratogenic and have high abortive potential. Vinca alkaloids, anthracyclines, 5-fluorouracil, cytarabine, taxanes and platinums appear to be relatively safe.

Chemotherapy during pregnancy needs to be modified according to the toxicity data of individual drugs. Chemotherapy is not given after 35 weeks and stopped 3 weeks prior to a planned delivery of the baby to allow for recovery of bone marrow function of the mother and foetus and for placental drug excretion from the foetus.

Management of specific cancers

Cervical cancer

The majority of cervical cancers in pregnancy are asymptomatic, diagnosed by abnormal cytology. Though atypical cytology is not uncommon in pregnancy, dysplastic changes are suspicious. Colposcopic biopsy is needed for suspected malignancy. Cone biopsy is associated with increased risk of vaginal bleeding, abortion, infection and premature delivery and hence used only for patients with suspicion of microinvasion or invasive disease. When indicated conization is done at 14–20 weeks of pregnancy. The majority of cervical cancer in pregnancy is squamous cell carcinoma (80–90%) and 80% present with stage IA–IIA disease. Staging includes physical examination, chest X-ray and MRI of abdomen and pelvis.

Cervical carcinoma-in-situ (CIN) can be managed with close follow-up with cytology and colposcopy. When invasive cancer is diagnosed the choice is between termination of pregnancy followed by treatment or postponing treatment until delivery. Cervical cancer with less than 3 mm invasion can be followed and delivered vaginally, whereas those with 3–5 mm invasion and/or lymphovascular invasion are delivered by caesarean section at 32–36 weeks.

Management of stage IA disease during the first trimester is debatable. Some advise radical hysterectomy for margin positive IA1 disease and IA2 disease. Patients with IA disease diagnosed during the second or third trimester can be followed up and treated only after delivery.

Patients with stage IB–IVA disease during the first and second trimesters of pregnancy are managed by termination of pregnancy and immediate treatment, whereas those diagnosed during the third trimester may be followed up until delivery after 32–38 weeks. Some patients diagnosed with cervical cancer in later second trimester and early third trimester can be treated with neoadjuvant chemotherapy until delivery of the baby. Radical treatment involves radical hysterectomy with lymphadenectomy or chemoradiotherapy.

There is no evidence to suggest that cervical cancer diagnosed during pregnancy has a worse outcome than those diagnosed when not pregnant, stage for stage.

Breast cancer

Breast cancer in pregnancy can occur at any time during pregnancy and within 12 months postpartum. The median age at diagnosis is 33 years and the commonest presentation is a painless palpable lump (80–95%). Presentation is similar to non-pregnant breast cancer. Diagnosis may be delayed accounting for a 2.5-fold increased risk of advanced cancers (40%) at presentation. Diagnosis is by mammogram, ultrasonography and non-enhanced MRI. Cytology may be difficult to interpret due to pregnancy associated changes and hence needle biopsy or open biopsy is diagnostic. The most common histological type is invasive ductal carcinoma (80–90%) followed by lobular carcinoma. The majority of tumours are high grade with axillary involvement (60–90%). Hormone receptors are negative in 40–70% and HER2 positive in 28–58%.

Staging investigations include chest X-ray, USS of abdomen and axilla and MRI if indicated. Serum alkaline phosphatase is doubled during pregnancy, but serum transaminases and CA 15-3 are unaffected.

In patients with non-metastatic disease, mastectomy and breast conserving surgery followed by radiotherapy (post partum) are accepted surgical treatments. Sentinel node biopsy using blue dye (risk of allergic reaction) and radioisotope are not advised (though the exposure is <5–15 mGy). Patients who need adjuvant chemotherapy can be safely treated after 12 weeks of gestation (1.3% risk of malformation) using anthracycline containing regime. Hormonal treatment and transtuzumab are not advised during pregnancy.

Patients with metastasis can be treated with chemotherapy after the first trimester. However, the issue of termination of pregnancy should be discussed in the appropriate context.

Most series suggest that pregnancy does not affect the natural course of illness or prognosis.

Melanoma

Common presenting symptoms are change in size and colour and bleeding or ulceration of pre-existing melanotic lesion as with melanomas diagnosed outside pregnancy (p. 234). Patients can present with lymphadenopathy and features of metastatic disease. Evaluation includes full clinical examination and skin examination followed by excisional biopsy, in limited disease. The commonest type is superficial spreading (74%) followed by nodular melanoma (16%). In the absence of clinical features of metastases, chest X-ray and USS abdomen are sufficient for staging.

The surgical excision margin is based on thickness of primary (p. 234). Treatment of metastatic melanoma is essentially palliative. Pregnancy termination should be discussed with the patient. Chemotherapy using dacarbazine or cisplatin can be given after the first trimester if the patient decides to continue with the pregnancy.

Studies suggest that the survival following a diagnosis of melanoma in pregnancy is the same as an equivalent stage of melanoma diagnosed in a non-pregnant woman.

Lymphomas

Lymphomas present with lymphadenopathy (70–80%) and B symptoms (20%). A small series suggested that in NHL there is a higher chance of presentation with extranodal manifestation (breast, GI, cervix and ovary). 70% of Hodgkin’s disease (HD) presents with stage I–II disease, whilst 70–80% of NHL present with stage III–IV disease.

Investigations include full blood count including ESR (raised in pregnancy), biochemistry, lymph node excision biopsy, bone marrow examination, USS of abdomen and pelvis. ENT examination, endoscopy and nervous system staging are done whenever indicated.

The most common type of HD is nodular sclerosis and 90% of pregnancy associated NHL are high grade.

When the diagnosis is made in the first trimester, termination of pregnancy is considered particularly in those with B-symptoms, bulky stage I–II, stage III–IV and high-grade lymphoma. If the patient refuses termination, single agent vinblastine may be given until the second trimester. The preferred regime for HD is ABVD and for NHL is CHOP (p. 298). Treatment may be delayed until delivery in low volume low-grade NHL. If treatment is needed for low-grade NHL, single agent chemotherapy or limited field radiotherapy is used.

When the diagnosis is made in the third trimester, treatment may be delayed until delivery at 32–35 weeks. Radiotherapy whenever indicated is generally delayed until delivery.

Prognosis of pregnancy associated lymphomas is similar to that of non-pregnant patients. The long term remission is 88% for HD and 45% for NHL.