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

This article have been viewed 1334 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.

Principles of management

Termination of pregnancy

Termination of pregnancy is an option when pregnancy itself is an obstacle to aggressive management of cancer and is associated with unacceptable risks for the health of mother and foetus. Termination of pregnancy in the first trimester is indicated only when treatment cannot be delayed and should take into consideration the curability of cancer, drugs to be used and wishes of the patient. The indications for termination generally are:

• Abdominal/pelvic tumour necessitating immediate treatment, especially if radiotherapy is needed.

• Aggressive disease course.

• Poor general condition of the patient.

• Inadvertent foetal exposure to more than 100 mGy during the first trimester.

Surgery

Surgery can be performed without major risk to the patient during the first two trimesters, but with a 1–2% risk of foetal loss, small risk of low birth weight (RR 1.5–2.0) and premature delivery. Foetal harm during surgery is due to various factors including placental transfer of drugs, intraoperative complications such as hypoxia, hypotension, and long-term supine positioning of mother during surgery causing placental underperfusion.

In the third trimester surgery after foetal maturation and delayed surgery until post-partum if appropriate are the options.

Intra-abdominal surgery is more likely to interfere with pregnancy. During major abdominal and pelvic surgery, continuous monitoring of the foetus is necessary. Measures to suppress premature labour and prophylactic treatment to improve foetal lung maturity should be undertaken if the surgery carries a risk of premature labour.

Timing of delivery and breast feeding

Delivery is generally planned after weeks 32–35 (earlier in modern neonatal units with better outcome for the baby) and 3 weeks after the last chemotherapy. Breast feeding is not recommended during chemotherapy, up to 2–4 weeks after completion of chemotherapy and during hormonal treatment.

Radiotherapy

The developing embryo or foetus is extremely sensitive to ionizing radiation, which can cause foetal loss, malformations, growth retardation and defects in intelligence. Radiotherapy is therefore contraindicated for abdominal and pelvic malignancies during pregnancy. Several studies support the use of radiotherapy for head and neck cancer, breast cancer and brain tumours. Radical radiotherapy to the head and neck and brain can be achieved with a foetal dose of less than 100 mGy (Box 19.2). During radiotherapy to the breast and chest wall, the dose to the foetus increases with gestational age. The foetal dose depends on the radiation field, dose, the distance between the edge of radiation field and foetus, and the machine and its shielding measures.

Box 19.2
Foetal radiation dose during radiotherapy

Radiotherapy	Foetal dose
Cervical cancer	45–50 Gy
Mantle field	0.014–0.13 Gy
Breast cancer	0.14–0.18 Gy
Brain tumour and head and neck cancer	0.0015–0.08 Gy

Radiotherapy should be delayed until postpartum if possible. If radiotherapy cannot be postponed the second trimester is the preferable time to deliver with appropriate precautions to keep foetal dose below 5–10 cGy.

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.

Postpartum care

The placenta should be send for histopathologic examination as there is risk of placental metastasis. Metastases can also occur in the foetus. In the absence of placental metastasis, optimal follow-up of a healthy baby is not known.

Future pregnancies

Most oncologists would recommend women not to become pregnant during follow-up for a period of 2–3 years depending on the type of cancer, risk of recurrence and patient’s age and wishes. There is no evidence to suggest that future pregnancies compromise survival.

Care of the baby

Anthracycline exposure in utero may affect heart development so this should be assessed as the child grows. With platinum-based chemotherapy during pregnancy, there is a concern that any non-renally excreted dose will be retained within the tissue which may affect later development, e.g. neural, although there is little evidence of this.

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.

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.

Ovarian cancer

Ovarian cancer is diagnosed rarely in pregnancy with 35% adenocarcinoma, 30% borderline ovarian tumour and 35% germ-cell/sex cord stromal tumour (most common dysgerminoma). Most of the borderline and germ cell tumours are diagnosed at an early stage.

Staging includes chest X-ray, abdominal and pelvic ultrasound and MRI if indicated (Figure 19.1). CA-125, beta-hCG and AFP are raised in pregnancy.

Figure 19.1 Pregnancy associated ovarian cancer – MRI shows uterus with foetus (white arrow heads) and omental thickening (arrow). Biopsy of the omental thickening confirmed serous papillary adenocarcinoma consistent with a primary peritoneal cancer.

Laparotomy or laparoscopy is indicated when there is suspicion of an ovarian lesion (persistent solid or complex mass lesion of >6 cm with associated ascites). Surgical principles follow that of ovarian cancer in non-pregnant women (p. 197). Maximum feasible cytoreduction is attempted and bilateral salpingo-oophorectomy after week 7 is feasible as the hormonal function will be taken up by placenta. Other option is neoadjuvant chemotherapy depending on the stage of gestation. In high-grade bulky tumours hysterectomy is also advisable. Chemotherapy may be administered after the first trimester.