1. Cancer in Pregnancy
March 2012
Prafull Ghatage
Gynecologic Oncologist
Tom Baker Cancer Centre
Calgary, CANADA.

2. Learning Objectives
• Incidence
• Investigations and management issues
• Risks of surgery
• Risks of radiotherapy
• Risks of chemotherapy
• Termination - ? Necessary / Advantageous
• If delivery - ? how / ? When
• Future pregnancies

3. The occurrence of cancer in pregnancy
is rare,
about 1 case per 1000 deliveries

4. The Dilemma
? Save the mother
? Save the baby
Malignant disease in pregnancy
complicates the management of
both cancer
and the pregnancy.

5. Is the potential life of an unborn child
more important than prolonging a life of a young woman?
And whose decision is this ?
?

6. Fetus Mother
Pregnancy
Risk

7. Management of cancer in pregnancy
There are not many options and
none of them are ideal

8. For women diagnosed with cancer
waiting for 40 weeks
could be a death sentence
particularly with high-grade, aggressive
or metastatic cancers.

9. To delay treatment until the child
can be safely delivered
• For mother this poses the risk that may be hard to quantify
• It also means that she will have to care for a very premature
baby while coping with the side-effects of cancer treatment
This option is more viable
the lower the risk posed by the cancer and
the more advanced the pregnancy
First option

10. To terminate the pregnancy to allow normal
treatment to go ahead
• This may be the safest option for the mother s health
• Unacceptable to some mothers
More likely to be considered early in pregnancy
Second option

11. To treat the cancer as effectively as possible
while continuing the pregnancy and trying to
minimize the risk for the fetus
Third option

12. Problems in treatment of cancer in pregnancy
• Late diagnosis
• Damaging effects of radiotherapy
• Consequences of chemotherapy

13. Delay in diagnostics
• Presenting symptoms often attributed to pregnancy
• Anatomical and physiological changes of
pregnancy may compromise the physical examination
• Tumor markers are increased in pregnancy
(beta HCG, AFP, CA 125... )
• Imaging techniques or invasive procedures

14. Cancer in pregnancy is often detected later
because the symptoms are masked by other,
usually physiological, body changes

15. Cancer in young women
Site Age 15-44 (%)
Cervix 35
Ovary 15
Lymphoma 23
Thyroid 50
Melanoma 27
Breast 15
Leukemia 10

16. Cancer incidence in Pregnancy
Site Est. incidence / 1000 pregnancies
Cervix
Non-invasive
Invasive
1.3-1.7
1.0
Breast 0.33 – 0.7
Melanoma 0.14
Ovary 0.10 ( 0.01%)
Thyroid Unknown
Lymphoma 0.01
Leukemia 0.01
Colon 0.20

17. Factors influencing the management
of pregnant women diagnosed with cancer
• Stage of cancer and associated prognosis
• Age of gestation- fetal viability
• Possible adverse effects of treatment on fetus
• Risk for mother from delay of therapy
• Risk for fetus of premature delivery
• Potential need to terminate the pregnancy

18. Diagnostic procedures that are
SAFE in pregnancy:
• Ultrasound
• Magnetic resonance imaging (MRI)

19. Difficulties in diagnostics & staging
Some techniques are unreliable
• Mammogram
• Blood tests- tumor markers
Some techniques are dangerous
• CT scan
• Radioisotope investigations
• Cervical conisation

20. Effective Radiation dose with
background radiation exposure
Procedure Radiation
dose in
millisieverts
Comparable
to
background
radiation for:
Additional lifetime
risk of fetal cancer
CXR 0.1 5 years Low
Abdominal
XR
2.2 9 months Very low
CT abd/
Pelvis
15 5 years Low
CT abd/pelvis
with contrast
30 10 years Moderate
Mammogram 0.4 7 weeks Very low
1 cGy = 1J/kg; 1 Sv = 1J/kg.

21. Three stages of Embryogenesis
• I – First 2 weeks – Blastocyst resistant to teratogens.
Blastocyst has NOT differentiated.
• II – Organogenesis – 3rd to 8th week. Maximal
teratogenesis. Ends by 13th week
• III – Increase in fetal and organ size. CNS development
complete by 16 weeks. Brain and gonadal tissue
will continue to develop. Teratogens will cause
IUGR but no organ malformation

22. Radiotherapy
• Contraindicated in pregnancy
• Possible in early pregnancy with lead
shielding
• Maybe also consider in late pregnancy for
the chest with shielding

23. Risks of radiotherapy
Therapeutic doses of 5000-6000 cGy
expose the fetus to 10 cGy in early pregnancy
and 200 cGy or more in later pregnancy
Doses over 2.5-5 cGy pose high risk
for malformation early in pregnancy
With 10 cGy the risk is 50%

24. Conception to days 9/10 Lethal
Weeks 2-6 Malformation
Growth retardation
Weeks 12-16 Mental and growth
retardation, microcephaly
Weeks 20-25 to birth Sterility, malignancies,
genetic disorders
Effects of radiotherapy

25. Risks of chemotherapy
Almost all drugs cross the placental
barrier to some extent
As chemotherapeutic drugs work
by inhibiting cell division,
they pose a risk to the developing fetus.

26. Risks of chemotherapy
• Spontaneous abortion
• Malformations
• Teratogenesis
• Mutations
• Carcinogenesis
• Organ toxicity
• Retarded development

27. First trimester
• Most likely in the 1st trimester.
• Fetal malformation rate 12.7-17% with single-drug
regimens and up to 25% with combination regimens
(cf - general population rate 1-3%)
• Low birth weight ~ 40%
Second and third trimester
• Relatively low risk
• It is preferable to wait until the development of CNS
is complete, around 16 weeks
Risks of chemotherapy

28. Delivery
If a baby is delivered within 2 weeks of the last
chemotherapy dose, there is a risk of a neutropenic baby
being born to a neutropenic mother
Breastfeeding
Breast feeding is not advisable for women who have
recently been on chemotherapy
Risks of chemotherapy

29. Lancet Oncology ,Amant et al, Feb 2012
• 68 pregnancies
• 236 cycles of chemotherapy
• Safe in the 2nd and 3rd trimester
• No association with CNS, Cardiac or Auditory morbidity.
Risks of chemotherapy

30. Pre-invasive and invasive cervical
cancer in pregnancy

31. Incidence of cervical pre-invasive
and invasive cancer in pregnant women
is similar to the incidence in general population
Pregnant women (4230) 0.17%
Non-pregnant women (107230) 0.18%
Bokhman JV, 1998.

32. The disease has been detected
during the pregnancy or postpartum
period
in 1.7 to 3.1%.
In reproductive age ≈10%
Creasman WT et al., 1970

33. Screening for invasive cervical cancer
should be performed during
the first antenatal examination
Harper DM, Roach MS. J Fam Pract, 1996; 42: 79-83

34. Management of abnormal cervical smear
during pregnancy
Pregnancy is not a contraindication for a pap smear
Abnormal cytology (5%)
Colposcopy
Biopsy

35. Indications for colposcopy
• Clinically SUSPICIOUS cervix
• Recurrent and otherwise unexplained
BLEEDING
• ABNORMAL pap

36. The aim of colposcopic examination
during the pregnancy
is to exclude invasion

37. Normal cervix in pregnancy

38. Normal cervix at 24 weeks

39. HPV in pregnancy

41. CIN III in pregnancy (ASCPP)

42. Microglandular Hyperplasia

43. Microinvasive cancer (ASCCP)

44. Early invasive cancer (ASCCP)

45. Decidual reaction

46. Conization in pregnancy
• MICROINVASION confirmed by biopsy
• Pap suggestive of INVASION
• ??? Unsatisfactory colposcopic
examination in a histologically proven
high grade lesion

47. Management after the histological finding in pregnancy
CIN Microinvasive cancer Invasive cancer
Conization
Postpone further Radical
diagnostic and hysterectomy
therapeutic procedures or
for post-partum period radiotherapy
Targeted biopsy

48. Treatment of cervical cancer in pregnancy
is affected
• by the stage of the disease
• by the age of gestation
• mother’s belief regarding pregnancy termination
• future childbearing desires

49. The treatment of invasive cervical cancer
in pregnancy
should proceed without regard for the fetus,
unless the lesion is diagnosed at a stage
close to fetal viability

50. Stage Ib/ IIa

51. Cervical cancer in pregnancy
I trimester: Surgery with embryo in utero
III trimester: Radical Caesarean hysterectomy
II trimester ? Medical and ethical problem

52. Invasive cervical cancer in second trimester
Before 20-24 weeks
Evacuating pregnancy by hysterotomy
and immediately after radical hysterectomy
After 24-28 weeks
Waiting for fetal maturity

53. Delay of treatment for 2-10 weeks
• Small tumor
• Stage < IIB
• Gestational age > 20 weeks
van Villet W i sar. Eur J Obst Gynec Reprod Biol, 1998; 79: 153-7

54. Adnexal masses during pregnancy
1:1000 deliveries
Most masses are benign. Malignant tumors are
generally low grade and stage with survival of
75%
Ovarian cancer 1 per 10.000 – 100.000 births
Ovarian tumors and the pregnancy

55. Most frequent types of ovarian tumors
in pregnancy
Benign cystic teratoma ................. 36%
Serous cystadenoma ................ 25%
Mucinous cystadenoma ................. 12%
Corpus luteum cyst ................. 5.5%
Malignant tumors ................ 4%

56. Malignant ovarian tumors and pregnancy
In non-pregnant woman 20% ovarian tumors
are malignant.
In pregnancy this percentage is
decreased to 5% ( 3% - 9.7%)
- - Epithelial carcinomas 33-65%
- - Germ-cell tumors 17-40%
- - Sex cord-stromal tumors 9-13%

57. Malignant ovarian tumors and pregnancy
• Only 16% of ovarian tumors detected in the first
trimester
• 20% diagnosed during CS or after delivery
• Almost 25% have an acute presentation (torsion)
If there are no complications, the best timing for surgery
of persistent ovarian mass in pregnancy is between
16 to18 weeks of gestation

58. If adnexal mass is < 8 cm, unilateral,
mobile and asymptomatic:
- observation and repeat U/S at 14 to 16
weeks.
If adnexal mass is > 8 cm, solid or of complex
appearance, bilateral or persists into 2nd
trimester:
- laparotomy
Management of ovarian mass in pregnancy

59. Breast cancer
• 3% of breast cancers is associated with pregnancy
• In the reproductive period patients, breast cancer
associated with pregnancy in 14% cases
• The incidence of breast cancer in pregnancy is 0.03
(1: 3000-1:10 000 pregnancies)
• Pregnant women have a 2.5 fold higher risk to
present with advanced cancer

60. Breast cancer in pregnancy
• Delay in starting the treatment is not recommended
• Mastectomy with axillary lymph node dissection
does not jeopardise pregnancy
• Conservative surgery ?
• Chemotherapy can be administered in pregnancy
• There is no consensus regarding radiotherapy
Survival is equal as in non-pregnant patients
if the stage of the disease is considered

61. Breast cancer in pregnancy
• Later pregnancies do not influence overall survival
• Next pregnancy should not be planned at least
for 2 years after treatment

62. The patient, her partner and her doctor
are required
to take a difficult decision without always a
clear answer
(rights of the fetus ≠ rights of the mother)
When should therapeutic abortion
be recommended?

63. Therapeutic abortion- general considerations
- Absence of guidelines.
- Final decision is not always easy
- Issue becomes more important when cancer
diagnosis is made during the first trimester
Most important parameters are:
- the stage
- the indication for treatment
- the curability of the disease.

64. Recommendations for therapeutic abortion
during the first trimester
1. Primary aggressive breast cancer
2. Advanced breast cancer
3. Stage III-IV aggressive NHL or
Hodgkin s disease
4. Acute leukemia

65. Conclusion
• Malignancy is rare in pregnancy
• Consideration of mother and fetus
• Close coordination also required between
patient, obstetrician, neonatologist and
oncologist