Transcript 0c482587cf29fe355877e5ebe570ade2

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.
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 breastfeeding. 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 mostcommon diagnosed 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 contraindicated.
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 supradiaphragmatic areas.
Thank you