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Cancer and chemotherapy with pregnancy. By Dr. Khattab KAEO Prof. & Head of Obstetrics and Gynaecology Department Faculty of Medicine, Al- Azhar University, Damietta. Incidence = 0.1-0.7%. Pregnant women account for 0.8% of all cancer cases in women.
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Cancer and chemotherapy with pregnancy By Dr. Khattab KAEOProf. & Head of Obstetrics and Gynaecology DepartmentFaculty of Medicine, Al-Azhar University, Damietta
Incidence = 0.1-0.7%. Pregnant women account for 0.8% of all cancer cases in women. The frequent cancers with pregnancy are malignant lymphomas, Hodgkin’s disease, leukaemias, breast cancer, melanoma and cancers of the cervix, thyroid and colon (&, recently, lung).
Effect of pregnancy No increased incidence, nor prognosis is adversely affected.
Effect on pregnancy Metastases to the placenta & fetus are rare; most of them are melanoma & leukemia. Most chemotherapeutic agents enter the fetal circulation.
The effect on the fetus & neonate depends on the timing of exposure: Pre-implantation:Blastocyst is resistant to teratogenic effects because circulation is not yet established. Either abortion occurs or nothing (all or none).
First trimester: Abortion and/or congenital malformation may occur. Fetal period:Microcephaly, MR & impaired learning. Most cases are noted with anti-metabolites & alkylating agents.
Other effects: IUGR & preterm labour. Long-term: Poor infant growth, decreased intellectual capacity & immunological status, increased risk of childhood cancer & reduced fertility.
The most potent teratogens are antifolates, thiouracils & pyrimidines Methotrexate is abortificient. The aminopterin syndrome includes cranial dysostosis, hypertelorism, widening of the nasal bridge, anomalies of the external ears & micrognathia.
Fortunately, there is no regimen for which an alternative agent cannot be substituted. Thus, avoid anti-metabolites throughout pregnancy. Vinca alkaloids (e.g. vincristine) & the antibiotics (e.g. Bleomycin, doxorubicin & daunorubicin) have little or no adverse fetal effects.
The benefits of chemotherapy outweigh the risks to the fetus. However, factors to be considered before administrating an agent include: 1- Tumour: Type, stage & sensitivity to chemotherapy. 2- Chemotherapy indication: curative or palliative. 3- Gestational age. 4- Opinion of parents. So, if cure is a goal & immediate institution is essential, administer without delay. Where high-dose intensive chemotherapy is needed, first deliver the fetus >28-32 w, better when maternal bl. counts are optimal.
Almost the same factors are considered for radiotherapy i.e. effectiveness, goal (curative or palliative), gestational age & risk to the fetus. The fetus can be protected from external scatter & leakage by shielding.
Fertility after treatment of cancer: It can be preserved by transplantation of cryo-preserved autologous ovarian tissue.
Breast cancer Parity reduces the risk, although there is evidence that the risk of breast cancer is transiently increased within 3 y of the last childbirth, followed by a subsequent decrease in risk.
Breast cancer Pregnancy also increases the risk of breast cancer developing in carriers of BRCA1 & BRCA2 mutations. Carriers of these mutations who have children are more likely to develop breast cancer by the age of 40 than carriers who are nulliparous, and each pregnancy is associated with increased risk of cancer. The well-known protective effect of pregnancy on NORMAL breast tissue is due to induction of stem cell differentiation. This is opposed by a growth acceleration effect on OCCULT cancers with increasing age.
Breast cancer Women who are pregnant at diagnosis of their breast cancer unfortunately have a worse prognosis with an increased risk of late-stage disease, particularly if the woman is aged ≤30. Some of this poor prognosis is due to advanced stage at diagnosis (difficulty in detecting pathology within a breast with physiological changes of pregnancy (firmness, nodularity & hypertrophy)or due to delays with treatment. Women becoming pregnant after treatment of their breast cancer have a similar, or even improved, prognosis as those who never become pregnant. There is no evidence that termination of pregnancy after diagnosis of breast cancer is necessary to improve prognosis. Breast feeding is not contraindicated.Breastfeeding confers a weak, but significant, protective effect that appears to be related to the duration of breast-feeding. Each year of breastfeeding confers a reduction of about 4% in breast cancer risk. However, during chemotherapy and radiotherapy women should not breast-feed.
Management The majority are high-grade, ER -ve, with a high proliferative rate & a high incidence of LN metastases. The obstetrician & the oncologist counsel the woman regarding early delivery followed by treatment Vs. commencement of therapy while continuing the pregnancy. Chemotherapy is considered because of the above-mentioned pathological features & because of the premenopausal age of the patient. However, unless there is evidence of metastasis, chemotherapy is delayed until the 2nd Tm (Tamoxifen abortion, birth defects & fetal deaths). If chemotherapy is necessary in the 1st trimester, termination of pregnancy may be proposed.
Management Radio-therapy is not absolutely contraindicated if the fetus is adequately shielded. CA-153 may be useful. Pregnancy should be delayed for at least 2 y (preferably 3 if the patient is <33 because of their higher local & distant relapse rates). Women with stage IV disease should not consider a pregnancy, and women with stage III disease should differ pregnancy for at least 5 years. Women with recurrent disease should not contemplate pregnancy because of the intensity of the required treatment and the poor prognosis.
Management Barrier contraception is recommended during tamoxifen use. Chemotherapy may cause premature ovarian failure, depending on the woman's age & the treatment regimen. Cyclophosphamide, an alkylating agent, can damage resting cells, while methotrexate and fluorouracil are cycle-specific i.e. they affect dividing cells. There is no evidence that any of these cytotoxic drugs used prior to a pregnancy produce any adverse effects on fetal development or the neonate. Now, treatment is unlikely to include oophorectomy for estrogen-receptor +ve stage II tumours.
Cervical cancer The mostcommondiagnosed cancer in preg There may be delay in diagnosis because bleeding is often attributed to the pregn. Routinely examine the cervix in any case of bleeding during pregnancy. Diagnosis in the first half of pregnancy = institution of curative treatment. Diagnosis in the second half of pregnancy, fetal survival is considered → caesarean hysterectomy. Vaginal delivery is contra-indicated.
Hodgkin’s disease Progress is less aggressive and treatment delay may be considered. If diagnosed in the first trimester, delay in commencing treatment should be considered unless the situation is life-threatening. In selected cases limited-field radiation may be considered to supra-diaphragmatic areas.
