International Journal of Reproduction, Contraception, Obstetrics and Gynecology
Reddi RP et al. Int J Reprod Contracept Obstet Gynecol. 2018 Aug;7(8):2989-2992
www.ijrcog.org pISSN 2320-1770 | eISSN 2320-1789
DOI: http://dx.doi.org/10.18203/2320-1770.ijrcog20183288
Review Article
Cancer in pregnancy
Reddi Rani P., Ashwini Vishalakshi L.*
Department of Obstetrics and Gynecology, Mahatma Gandhi Medical College and Research Institute, Sri Balaji
Vidyapeeth University, Pilliyarkuppam, Pondicherry, Tamil Nadu, India
Received: 28 May 2018
Accepted: 26 June 2018
*Correspondence:
Dr. Ashwini Vishalakshi L.,
E-mail: [email protected]
Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Cancer in pregnancy though rare is a challenging problem both for patient and obstetrician. It is on rise though
pregnancy does not predispose cancer. Persistent symptoms like vomiting, abdominal pain, discharge etc should be
thoroughly evaluated by clinical USG and if necessary by MRI if there is a strong suspicion of malignancy to detect
early and treat promptly. A multidisciplinary discussion is necessary. Management depends on type of malignancy,
stage, risk factors, histopathology and gestational age. Carcinoma of breast and cervix are common malignancies that
occur in pregnancy. It is preferable to postpone surgery and CT till first trimester is completed. A through counseling
is essential regarding termination of pregnancy, type of treatment and its effects in mother and fetus and prognosis.
Aim should be curative treatment to the mother with some modifications in the treatment keeping in mind maternal
and fetal safety.
Keywords: Cancer, Chemotherapy, Pregnancy, Radiotherapy, Surgery
INTRODUCTION personal and emotional factors vary between patients and
makes management difficult.
Cancer during pregnancy is a special challenge as cancer
or its treatment may affect not only the pregnant woman DIAGNOSIS DURING PREGNANCY
but also fetus and needs proper counseling and
multidisciplinary approach. It is the second most common Cancer diagnosis in pregnancy poses a very difficult
cause of death in women during their reproductive age challenge to woman, her family and doctor. The benefits
and complications between 0.02%-0.1% of all of diagnostic workup, treatment modalities like surgery,
pregnancies.1 The incidence is increasing due to radiotherapy, and chemotherapy (CT) has to be weighed
concomitant increase in the age of child bearing. The carefully against the risks to the fetus.
most common cancers seen during pregnancy are breast
and cervical carcinomas. Diagnosis may be delayed as symptoms of pregnancy like
nausea, vomiting, breast changes, abdominal pain,
Others which are rarely found are lymphomas, Hodgkin’s anemia, bleeding or vaginal discharge all these
disease, malignant melanoma, ovarian tumors especially physiological changes may mimic malignancy symptoms.
germ cell and borderline epithelial tumors etc. Curative
treatment of the mother is the main priority and should So careful clinical examination is necessary for persisting
adhere to standard treatment protocols with some or worsening symptoms, so that delay in diagnosis and
modifications without causing harm to the fetus. Ethical, treatment can be avoided. Clinical examination also may
be difficult due to gravid uterus and breast changes.
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Reddi RP et al. Int J Reprod Contracept Obstet Gynecol. 2018 Aug;7(8):2989-2992
Imaging techniques are restricted to ultrasound and MRI Fetal anoxia can occur during surgery due to maternal
and also there is a decrease in utility of tumor markers. hypotension, deep general anesthesia, hypovolemia and
All these factors are contributing for delay in diagnosis venacaval compression. Fetal oxygenation during surgery
and also there is hesitance in starting antineoplastic is very important. Venacaval compression can be avoided
treatment in pregnancy. There is a need to weigh the risks by left lateral tilt and maintaining PaO2 and PaCO2 and
and benefits for both maternal and fetal wellbeing. uterine blood flow. A stable maternal condition is the best
guarantee for fetal wellbeing. One of the earliest signs of
STAGING OF CANCER IN PREGNANCY maternal distress is fetal distress.4 There is a need for
continuous cardiotocographic monitoring during surgery
It should be comprehensive staging using clinical and especially if she is in the third trimester and if there is any
imaging modalities like ultrasound and MRI and also abnormality caesarean section can be done at the same
avoiding CT scan and radiographic examination. If time.
deemed necessary radiation exposure should be as low as
reasonably achievable to avoid detrimental effects on the Tocolytics are indicated to prevent abortion and preterm
fetus. A dose of 100mGy has detrimental effects on the labor especially in abdominal surgery where there is a
fetus causing lethality, malformations and mental possibility of uterine manipulation. Adequate analgesia is
retardation.2 For pathological confirmation tissue biopsy required postoperatively. Surgery maybe diagnostic or
is more accurate than fine needle aspiration cytology. therapeutic which may be associated with prematurity
Reporting pathologist has to keep in mind the either due to surgical procedure or due to exposure to
physiological hyperproliferative changes while anesthesia.5 In case of laparotomy midline vertical
reporting.3 incision is preferred for optimal exposure. Laparoscopic
approach is preferred if feasible during pregnancy
GENERAL PRINCIPLES OF TREATMENT depending on the size of uterus and modification has to
be done for safe entry into abdomen.6 Laparoscopy
After diagnosis of cancer patient and relatives should be becomes technically difficult after 26-28 weeks of
counseled regarding decision making, explaining her gestation due to gravid uterus and in these cases
about her stage of disease, effects of treatment on mother laparotomy is preferred.7 Expert consensus meeting
and fetus, regarding pregnancy termination, iatrogenic recommended the prerequisites for treating malignancy
prematurity or intentional delay in treatment and during pregnancy with laparoscopy are; a maximal
prognosis. Treatment should be individualized and should laparoscopic procedure time of 90 minutes, a
be counseled regarding the risk of recurrence with future pneumoperitoneum with a maximum intra-abdominal
pregnancies and need for continuous surveillance. The pressure of 10-13mmHg, open introduction and
modalities of treatments are surgery, radiotherapy (RT), experienced surgeon.8
chemotherapy (CT), usually combinations of two or three
modalities in advanced stages. RADIOTHERAPY DURING PREGNANCY
SURGERY Radiotherapy during pregnancy to cancers other than
genital tract malignancies is safe when pregnancy is still
Though it can be done in all trimesters, avoid if possible early, and adequate distance exists between radiation
during first trimester. Some modifications have to be field and the fetus and fetal radiation dose is less than 100
done in anesthesia and surgery without compromising the mGy. Treatment plan has to be modified by changing
curative treatment and considering the fetal and maternal field angles, reducing field size, modifying the beam
safety and prevention of obstetrical complications like energy etc. It is important to calculate the fetal dose by
abortion and preterm labor. Surgery depends on the age measurements in a phantom before treatment is given.
of the patient, gestational age of pregnancy, type of Montecarlo methodology can be used to evaluate and
malignancy, stage of disease and histopathology report. estimate fetal dose.9 Long-term follow up of children
exposed to radiation in uterus suggests that RT to upper
PREOPERATIVE PREPARATION body parts before third trimester and with shielding of
pregnancy does not induce fetal harm.
A proper preoperative oxygenation, antacids and
premedication are necessary to minimize aspiration CHEMOTHERAPY DURING PREGNANCY
pneumonitis and anxiety. Antibiotics prophylactic/
therapeutic doses should be given depending on the Chemotherapy during first trimester of pregnancy may
specific surgical procedure. Antibiotics should be chosen increase the risk of spontaneous abortions, fetal death and
which are safe in pregnancy and lactation. They are at major congenital malformations. The teratogenic effects
high risk for thromboembolism due to pregnancy, depend on type of chemotherapeutic agent, dosage,
malignancy, surgery and immobilization and should be gestational age at administration and cumulative effect.
advised thromboprophylaxis with unfractionated or low The most vulnerable period is 2-8 weeks when
molecular weight heparin. organogenesis occurs. First trimester exposure has been
associated with 10-20% risk of major malformation
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Reddi RP et al. Int J Reprod Contracept Obstet Gynecol. 2018 Aug;7(8):2989-2992
which can reduce to about 6% when folate antagonists delivery or pregnancy continued 2-3 weeks following
are excluded.10 anticancer treatment if it is feasible for bone marrow
recovery.14 As cancer chemotherapeutic drugs are
Cardonic et al in a review of 376 cases of fetuses exposed excreted into milk, they should be avoided during
to CT in utero after organogenesis demonstrated 5% fetal lactation or if it is essential to give CT avoid
death, 1% neonatal death, 5% preterm delivery, 7% breastfeeding.
IUGR and 4% transient myelosuppression.11
SOGC GUIDELINES FOR CT IN PREGNANCY
Administration of CT during second and third trimester
of pregnancy is associated with major congenital 1. Most of the women in childbearing age are
malformations but may be associated with increased risk postponing their pregnancy, so more cases are being
of IUGR, preterm and stillbirths. CT is advised only after diagnosed with cancer in pregnancy. Doctor should
12-14 weeks of pregnancy because of teratogenicity risks examine the patient’s risk of pregnancy and desire to
and also by then placenta develops which acts as a barrier prevent pregnancy during CT.
and protects the fetus. Administration of CT during 2. CT agents used to combat cancer cases cross the
pregnancy is not an indication for termination of placenta and may adversely affect embryogenesis by
pregnancy and it allows timely maternal treatment affecting cell division and results in major congenital
without delay and helps in prevention of iatrogenic malformations. Exposure to CT drugs after first
prematurity. trimester is not associated with increased risk of
malformations but with increased risk of stillbirths
Alkylating agents IUGR and fetal toxicity.
3. Decision about the best course of management in
Cyclophosphomide is commonly used for the treatment pregnancy including timing of delivery should
of breast cancer, ovarian cancer and non hodgkins balance maternal and fetal risks.
lymphoma which act directly on cell DNA to prevent 4. They should be optimally managed by a
rapidly replicating cells from reproducing. In an analysis multidisciplinary team.15
of outcome of 61 patients treated for different
malignancies during second and third trimester found 59 OBSTETRIC AND PERINATAL MANAGEMENT
infants were born with no malformations.12
Initial ultrasound at booking should be done to evaluate
Platinum compounds the fetal gestational age, anomalies, later for fetal growth
and development by regular fetal monitoring. Cervical
Cisplatin and carboplatin are the most commonly used length should be measured especially in cases of early
drugs in carcinoma cervix, ovarian cancer, lung cancer carcinoma cervix where cone biopsy/ radical
etc. Their use in second and third trimester was not trachelectomy was done to assess for cervical
associated with adverse fetal effects. incompetence. If CT is ongoing delivery should be
planned 3 weeks after the last cycle of CT during
Antimetabolites pregnancy to avoid accumulation in the neonate and also
to avoid problems associated with hematopoietic
Methotrexate, 5-flurouracil, mercaptopurine etc. come suppression during delivery and for the same reason CT
under this category and cause inhibition of cellular should not be administered after 35-37 weeks since
metabolism. Methotrexate exposure during first trimester spontaneous labor can occur any time.
can cause malformations like cranial dysostosis,
hypertelorism, wide nasal bridge, micrognathia etc.13 Mode of delivery is vaginal in majority of cases except in
carcinoma cervix and where there is metastatic disease in
Anthracyclines long bones where there may be a risk of fracture due to
lithotomy position. It is also indicated in cases where
These include doxorubicin, epirubicin ect. Cardmock et there is CNS metastasis causing increased intracranial
al observed pregnancy outcome in 118 patients treated for pressure due to active pushing in vaginal delivery.8
breast cancer and lymphoma during second and third Caesarean section is also indicated in cases of vulval
trimester and found five abnormal fetuses with cancer where there is extensive scarring and vulval
anomalies.11 Plant alkaloids like taxanes are also safe trauma.
during second and third trimester.
Rarely placental metastasis has been reported. Proven
Safety of molecularly targeted agents use like tyrosine metastasis to the fetus is rare. Malignancies spreading to
kinase inhibitors, monoclonal antibody, rituximab etc. products of conception are melanoma (32%), leukemia
has not been established in pregnancy. and lymphoma (5%), breast cancer (13%), lung cancer
(11%), gynecological cancer (3%) etc.16 In those having
Timing of delivery should be planned to avoid placental metastases the infant should be monitored for
myelosupression. It should be stopped 2-3 weeks before development of malignant disease. Breast feeding is
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Reddi RP et al. Int J Reprod Contracept Obstet Gynecol. 2018 Aug;7(8):2989-2992
allowed unless CT is ongoing postpartum or administered 5. Cohen-Kerem R, Railton C, Oren D, Lishner M,
in the last week before delivery. Koren G. Pregnancy outcome following non-
obstetric surgical intervention. Am J Surgery.
LONG TERM FOLLOW-UP OF CHILDREN 2005;190(3):467-73.
6. Yumi H. Guidelines for diagnosis, treatment, and use
Recent evidence suggests CT is safe beyond first of laparoscopy for surgical problems during
trimester. Aviles et al reported in a follow up of mean pregnancy. Surg Endosc. 2008;22(4):849-61.
18.7 yrs of 84 children born to mothers of hematological 7. Pearl J, Price R, Richardson W, Fanelli R. Guidelines
malignancies who received CT during pregnancy and for diagnosis, treatment, and use of laparoscopy for
found no congenital neurological or psychological surgical problems during pregnancy. Surg Endosc.
abnormalities and they had good learning and educational 2011;25(11):3479.
performances.17 Another concern is the potential effect of 8. Amant F, Halaska MJ, Fumagalli M, Steffensen KD,
anthracyclines on the fetal heart. These are commonly Lok C, Van Calsteren K, et al. Gynecologic cancers
used in breast and hematological cancers. Aviles et al in pregnancy: guidelines of a second international
reported follow up of 81 children exposed to cytotoxic consensus meeting. Int J Gynecol Cancer.
drugs including anthracyclines in utero found no 2014;24(3):394-403.
evidence of cardiac disease and echo and fractional 9. Bednarz B, Xu XG. A feasibility study to calculate
shortening were normal.18 unshielded fetal doses to pregnant patients in 6‐MV
photon treatments using Monte Carlo methods and
CONCLUSION anatomically realistic phantoms. Med Physics.
2008;35(7 Part1):3054-61.
Carcinoma in pregnancy is rare. Management is a 10. Doll DC, Ringenberg QS, Yarbro JW. Antineoplastic
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Treatment should be multidisciplinary. Optimizing the 1989;16(5):337-46.
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surgery CT and RT. Surgery and CT are better preferred analysis of 215 patients emphasizing the obstetrical
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Funding: No funding sources Send to J Obstet Gynaecol Can. 2013;35(3):263-278
Conflict of interest: None declared 16. Alexander A, Samlowski WF, Grossman D,
Ethical approval: Not required Bruggers CS, Harris RM, Zone JJ, Noyes RD, et al.
Metastatic melanoma in pregnancy: risk of placental
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