Cancer and chemotherapy Cancer and chemotherapy with pregnancywith pregnancy

By By

Dr. Khattab KAEODr. Khattab KAEO Prof. & Head of Obstetrics and Gynaecology Prof. & Head of Obstetrics and Gynaecology

DepartmentDepartmentFaculty of Medicine, Al-Azhar University, Faculty of Medicine, Al-Azhar University,

DamiettaDamietta

IncidenceIncidence = 0.1-0.7%. = 0.1-0.7%.

Pregnant women account for 0.8% of all Pregnant women account for 0.8% of all cancer cases in women.cancer cases in women.

The frequent cancers with pregnancy The frequent cancers with pregnancy are malignant lymphomas, Hodgkinare malignant lymphomas, Hodgkin’’s s

disease, leukaemias, breast cancer, disease, leukaemias, breast cancer, melanoma and cancers of the cervix, melanoma and cancers of the cervix, thyroid and colon (&, recently, lung). thyroid and colon (&, recently, lung).

Effect of pregnancyEffect of pregnancy

No increased incidence, No increased incidence, nor prognosis is nor prognosis is adversely affected. adversely affected.

Effect on pregnancyEffect on pregnancy Metastases to the Metastases to the

placenta & fetus are placenta & fetus are rare; most of them are rare; most of them are melanoma & leukemia. melanoma & leukemia.

Most chemotherapeutic Most chemotherapeutic agents enter the fetal agents enter the fetal circulation. circulation.

The effect on the fetus & neonate The effect on the fetus & neonate depends on the depends on the timingtiming of exposure: of exposure:

Pre-implantation:Pre-implantation: Blastocyst is Blastocyst is resistant to teratogenic effects resistant to teratogenic effects because circulation is not yet because circulation is not yet established. Either abortion occurs established. Either abortion occurs or nothing (all or none). or nothing (all or none).

First trimester:First trimester: Abortion and/or Abortion and/or congenital malformation may occur. congenital malformation may occur.

Fetal period:Fetal period: Microcephaly, MR & Microcephaly, MR & impaired learning. Most cases are impaired learning. Most cases are noted with anti-metabolites & noted with anti-metabolites & alkylating agents. alkylating agents.

Other effects: IUGR & preterm Other effects: IUGR & preterm labour. labour.

Long-term: Poor infant growth, Long-term: Poor infant growth, decreased intellectual capacity decreased intellectual capacity & immunological status, & immunological status, increased risk of childhood increased risk of childhood cancer & reduced fertility. cancer & reduced fertility.

The most potent teratogens are The most potent teratogens are antifolates, thiouracils & pyrimidinesantifolates, thiouracils & pyrimidines

Methotrexate is abortificient. Methotrexate is abortificient.

The aminopterin syndrome includes The aminopterin syndrome includes cranial dysostosis, hypertelorism, cranial dysostosis, hypertelorism, widening of the nasal bridge, widening of the nasal bridge, anomalies of the external ears & anomalies of the external ears & micrognathia. micrognathia.

Fortunately, there is no regimen Fortunately, there is no regimen for which an alternative agent for which an alternative agent cannot be substituted. cannot be substituted.

Thus, avoid anti-metabolites Thus, avoid anti-metabolites throughout pregnancy. throughout pregnancy.

Vinca alkaloids (e.g. vincristine) Vinca alkaloids (e.g. vincristine) & the antibiotics (e.g. & the antibiotics (e.g. Bleomycin, doxorubicin & Bleomycin, doxorubicin & daunorubicin) have little or no daunorubicin) have little or no adverse fetal effects. adverse fetal effects.

The benefits of chemotherapy outweigh the The benefits of chemotherapy outweigh the risks to the fetus.risks to the fetus.

However, factors to be considered before However, factors to be considered before administrating an agent include: administrating an agent include:

1- Tumour: Type, stage & sensitivity to 1- Tumour: Type, stage & sensitivity to chemotherapy. chemotherapy.

2- Chemotherapy indication: curative or 2- Chemotherapy indication: curative or palliative. palliative.

3- Gestational age.3- Gestational age.4- Opinion of parents. 4- Opinion of parents.

So, if cure is a goal & immediate institution is So, if cure is a goal & immediate institution is essential, administer without delay. Where essential, administer without delay. Where high-dose intensive chemotherapy is needed, high-dose intensive chemotherapy is needed, first deliver the fetus >28-32 w, better when first deliver the fetus >28-32 w, better when maternal bl. counts are optimal. maternal bl. counts are optimal.

Almost the same factors are Almost the same factors are considered for radiotherapy considered for radiotherapy i.e. effectiveness, goal i.e. effectiveness, goal (curative or palliative), (curative or palliative), gestational age & risk to the gestational age & risk to the fetus. fetus.

The fetus can be protected The fetus can be protected from external scatter & from external scatter & leakageleakage by shielding. by shielding.

Fertility after treatment of Fertility after treatment of cancer:cancer:

It can be preserved by It can be preserved by transplantation of transplantation of cryo-preserved cryo-preserved autologous ovarian autologous ovarian tissue. tissue.

Breast cancerBreast cancer Parity reduces the risk, Parity reduces the risk, although there is although there is evidence that the risk of evidence that the risk of breast cancer is breast cancer is transiently increased transiently increased within 3 y of the last within 3 y of the last childbirth, followed by a childbirth, followed by a subsequent decrease in subsequent decrease in risk.risk.

Breast cancerBreast cancer Pregnancy also increases the risk of breast Pregnancy also increases the risk of breast

cancer developing in carriers ofcancer developing in carriers of BRCA1 BRCA1 && BRCA2BRCA2 mutations. mutations.

Carriers of these mutations who have Carriers of these mutations who have children are more likely to develop breast children are more likely to develop breast cancer by the age of 40 than carriers who cancer by the age of 40 than carriers who are nulliparous, and each pregnancy is are nulliparous, and each pregnancy is associated with increased risk of cancer. associated with increased risk of cancer.

The well-known protective effect of The well-known protective effect of pregnancy on NORMAL breast tissue is pregnancy on NORMAL breast tissue is due to induction of stem cell due to induction of stem cell differentiation. This is opposed by a differentiation. This is opposed by a growth acceleration effect on OCCULT growth acceleration effect on OCCULT cancers with increasing age.cancers with increasing age.

Breast cancerBreast cancer Women who are pregnant at diagnosis of their breast Women who are pregnant at diagnosis of their breast

cancer unfortunately have a worse prognosis with an cancer unfortunately have a worse prognosis with an increased risk of late-stage disease, particularly if the increased risk of late-stage disease, particularly if the woman is aged ≤30. Some of this poor prognosis is due woman is aged ≤30. Some of this poor prognosis is due to advanced stage at diagnosis (difficulty in detecting to advanced stage at diagnosis (difficulty in detecting pathology within a breast with physiological changes of pathology within a breast with physiological changes of pregnancy (firmness, nodularity & hypertrophy) or due pregnancy (firmness, nodularity & hypertrophy) or due to delays with treatment.to delays with treatment.

Women becoming pregnant after treatment of their Women becoming pregnant after treatment of their breast cancer have a similar, or even improved, breast cancer have a similar, or even improved, prognosis as those who never become pregnant.prognosis as those who never become pregnant.

There is no evidence that termination of pregnancy after There is no evidence that termination of pregnancy after diagnosis of breast cancer is necessary to improve diagnosis of breast cancer is necessary to improve prognosis. prognosis.

Breast feeding is not contraindicated.Breast feeding is not contraindicated. Breastfeeding Breastfeeding confers a weak, but significant, protective effect that confers a weak, but significant, protective effect that appears to be related to the duration of breast-feeding. appears to be related to the duration of breast-feeding. Each year of breastfeeding confers a reduction of about Each year of breastfeeding confers a reduction of about 4% in breast cancer risk. However, during 4% in breast cancer risk. However, during chemotherapy and radiotherapy women should not chemotherapy and radiotherapy women should not breast-feed. breast-feed.

ManagementManagement The majority are high-grade, ER -ve, with a The majority are high-grade, ER -ve, with a

high proliferative rate & a high incidence of high proliferative rate & a high incidence of LN metastases. The obstetrician & the LN metastases. The obstetrician & the oncologist counsel the woman regarding oncologist counsel the woman regarding early delivery followed by treatment Vs. early delivery followed by treatment Vs. commencement of therapy while continuing commencement of therapy while continuing the pregnancy. the pregnancy.

Chemotherapy is considered because of the Chemotherapy is considered because of the above-mentioned pathological features & above-mentioned pathological features & because of the premenopausal age of the because of the premenopausal age of the patient. However, unless there is evidence of patient. However, unless there is evidence of metastasis, chemotherapy is delayed until metastasis, chemotherapy is delayed until the 2nd Tm (Tamoxifen the 2nd Tm (Tamoxifen abortion, birth abortion, birth defects & fetal deaths). If chemotherapy is defects & fetal deaths). If chemotherapy is necessary in the 1st trimester, termination of necessary in the 1st trimester, termination of pregnancy may be proposed. pregnancy may be proposed.

ManagementManagement Radio-therapy is not absolutely Radio-therapy is not absolutely

contraindicated if the fetus is contraindicated if the fetus is adequately shielded. adequately shielded.

CA-153 may be useful.CA-153 may be useful.Pregnancy should be delayed for at least Pregnancy should be delayed for at least

2 y (preferably 3 if the patient is <33 2 y (preferably 3 if the patient is <33 because of their higher local & distant because of their higher local & distant relapse rates). Women with stage IV relapse rates). Women with stage IV disease should not consider a disease should not consider a pregnancy, and women with stage III pregnancy, and women with stage III disease should differ pregnancy for at disease should differ pregnancy for at least 5 years. Women with recurrent least 5 years. Women with recurrent disease should not contemplate disease should not contemplate pregnancy because of the intensity of pregnancy because of the intensity of the required treatment and the poor the required treatment and the poor prognosis. prognosis.

ManagementManagement Barrier contraception is recommended during Barrier contraception is recommended during

tamoxifen use. tamoxifen use. Chemotherapy may cause premature ovarian Chemotherapy may cause premature ovarian

failure, depending on the woman's age & the failure, depending on the woman's age & the treatment regimen. treatment regimen.

Cyclophosphamide, an alkylating agent, can Cyclophosphamide, an alkylating agent, can damage resting cells, while methotrexate damage resting cells, while methotrexate and fluorouracil are cycle-specific i.e. they and fluorouracil are cycle-specific i.e. they affect dividing cells. affect dividing cells.

There is no evidence that any of these There is no evidence that any of these cytotoxic drugs used prior to a pregnancy cytotoxic drugs used prior to a pregnancy produce any adverse effects on fetal produce any adverse effects on fetal development or the neonate. development or the neonate.

Now, treatment is unlikely to include Now, treatment is unlikely to include oophorectomy for estrogen-receptor +ve oophorectomy for estrogen-receptor +ve stage II tumours. stage II tumours.

Cervical cancerCervical cancer The mostcommon The mostcommon diagnoseddiagnosed cancer in preg cancer in preg

There may be delay in diagnosis because There may be delay in diagnosis because bleeding is often attributed to the pregn.bleeding is often attributed to the pregn.

Routinely examine the cervix in any case of Routinely examine the cervix in any case of bleeding during pregnancy. bleeding during pregnancy.

Diagnosis in the first half of pregnancy = Diagnosis in the first half of pregnancy = institution of curative treatment. institution of curative treatment.

Diagnosis in the second half of pregnancy, Diagnosis in the second half of pregnancy, fetal survival is considered fetal survival is considered → caesarean → caesarean hysterectomyhysterectomy. Vaginal delivery is contra-. Vaginal delivery is contra-indicated. indicated.

Hodgkin’s diseaseHodgkin’s disease

Progress is less aggressive and Progress is less aggressive and treatment delay may be considered.treatment delay may be considered.

If diagnosed in the first trimester, If diagnosed in the first trimester, delay in commencing treatment delay in commencing treatment should be considered unless the should be considered unless the situation is life-threatening. situation is life-threatening.

In selected cases limited-field radiation In selected cases limited-field radiation may be considered to supra-may be considered to supra-diaphragmatic areas. diaphragmatic areas.

Thank youThank you