This document discusses cancer diagnosis and treatment during pregnancy. It notes that cancer during pregnancy is rare but may increase due to delayed childbearing. Data on outcomes after cancer treatment during pregnancy is limited due to low prevalence, high rates of pregnancy termination, and decisions not to treat during critical fetal periods. The most common cancers seen in pregnancy are breast, hematologic, skin, cervical, ovarian, and colorectal cancers. Radiographic and surgical procedures pose minimal risk after the first trimester. Chemotherapy also poses low risk after the first trimester, though some drugs like alkylating agents carry higher risk. Outcomes of cancer diagnosed and treated during pregnancy are generally similar to non-pregnant patients.

2. 2

3. 3

4.  Cancer in pregnancy is rare (0.02 - 0.1%)
 Because of rise in delayed child-bearing, rates of
cancer in pregnancy are expected to rise.
 Data of pregnancy outcomes following cancer Rx
are limited due to:
 Low prevalence of cancer during pregnancy,
 High rates of pregnancy terminations in women with
cancer, &
 Decision not to treat during critical foetal periods.
4

5. 5
 Breast cancer,
 Haematologic cancers (leukaemias &
lymphomas),
 Dermatologic cancer (M. Melanoma)
 Cervical cancer,
 Ovarian cancer,
 Colo-rectal cancer.

6. 6
Cancer, fertility and pregnancy: ESMO Clinical Practice Guidelines for diagnosis,
treatment and follow-up (2010)

7. 7
Marker Malignancy Normal Level Effects of Pregnancy
CA125 Ov. papillary serous cancer
BOTs
<35 U/mL Elevated in first TM
hCG GTD <5 IU/mL Peak at 14-16 wks,12,000-270,000
AFP Malig Germ cell ov. tumours
HCC
<15 ng/mL Peak at 13 wks, (200-300)
LDH Dysgerminoma
Liver tumours
45-90 U/L Fluctuates minimally
Inhibin Granulosa cell ov. tumours 33-45 pg/mL Increases in PET
Testos. Sertoli cell ov. Tumours 30-95 ng/dL Rises 4 - 9 folds
DHEA-S Adrenal gland tumours 35-430 mcg/dL May increase up to 700
CEA Ov. Mucinous carcinoma
Pseudo-myxoma peritoneii
Colo-rectal carcinoma
<5 ng/mL May be slightly elevated
CA27.29 Breast cancer <38 U/mL Not well studied
CA15.3 Breast cancer <40 U/mL Elevated in 3rd TM (one study)
CA19.9 Panceriatic cancer < 40 U/mL Not well studied
PRL Pituitary prolactinoma <20 ng/mL 20-400
Total
Thyroxin
Thyroid carcinoma 5-12 mcg/dL Increased (d.t. ↑thyroxin binding
gl)

8.  Most procedures that do not interfere with the
reproductive tract are well tolerated by both
mother and foetus.
 Operative procedures are better to be deferred
until > 12 - 14 wks (to  abortion risks).
 However, surgery is to be performed regardless
of GA if maternal well-being is endangered.
8

9.  Most diagnostic radiographic procedures  very
low x-ray exposure (shouldn’t be delayed if
needed).
 Side effects usually occur after 5 Rads (0.05 Gy).
 The most susceptible period is 18-38 days, (& the
1st TM in general).
 Non-ionizing radiation (U/S & MRI) are safe.
9

10.  CT (not including the uterus) negligible foetal effect
 Standard single-pass CT (through the uterus) with IV
& oral contrast  foetal exposure to < 25 mGy. (<
2.5 Rads)  only small  risk ( 1%) of childhood
cancer (leukaemia).
 MRI with IV gadolinium is an FDA class C agent &
should NOT be given in pregnancy. It crosses the
placenta into the foetal circulation.
10

11. Procedure Fetal exposure
Chest X-ray (2 views) 0.02 – 0.07 mrad
Abdominal film ( 2 views) 1000 mrad
IVP > 1 rad ( acc to no. of films)
Hip film (single view) 7-20 mrad
Ba enema or small bowel series 2-4 rads
CT scan of Head or Chest < 1 rad
CT scan of Abd & lumbar spines 3.5 rad
CT pelvimetry 250 mrad 11

12.  The most susceptible period is during the 1st TM,
however, there is no GA considered safe for
therapeutic radiation exposure.
 Therapeutic radiation results in significant foetal
exposure. The amount depends on the dose,
tumour location, & field size.
12

13.  Effect= cell death, teratogenicity, carcinogenesis,
& genetic effects or germ cell mutations (gonads).
 Adverse foetal effects are microcephaly & MR.
Even late exposure may  IUGR & brain damage.
 Radiation to maternal abdomen is contraindicated
because of a high risk of foetal death or damage.
 Supra-diaphragmatic radio-x is relatively safe with
abdominal shielding (as in head & neck cancers).
 BUT: In breast cancer, significant scattered doses
can affect the foetus.
13

14.  Most of cytotoxic agents cross the placenta
because of their relatively low molecular weight.
 Embryonic (1st TM) exposure to cytotoxic drugs
 abortion & major malformations in 10 - 20 % of
cases (organogenesis).
 Most vulnerable period is 2-8 weeks.
 After 1st TM, most anti-neoplastic drugs is not
associated with major congenital malformations.
 Foetal concerns include malformations, IUGR,
MR, LBW, IUFD & risk of future malignancies.
14

15. 1. Alkylating agents (Cyclophosphamide)  high risk.
2. Platinum compounds (Cisplatin, carboplatin)  in 2nd & 3rd TM  not
ass. with any pattern or increased risk of adverse foetal effects.
3. Antimetabolites (methotrexate, 5-fluorouracil, aminopterin, cytarabine,
tioguanine, & mercaptopurine)
 Methotrexate in 1st TM  ass. with malformations similar to the aminopterin
syndrome, including cranial dysostosis with delayed ossification, hypertelorism, wide
nasal bridge, micrognathia, & ear anomalies.
 So, it shouldn’t be considered a 1st-line therapy, & not to be used at any stage of preg.
 5-fluorouracil is not one of the first-line agents recommended, but it has not been
ass. with any increased risk for malformation in 2nd & 3rd TM .
4. Anti-tumour antibiotics (Bleomycin)  in 2nd & 3rd TM  not ass. with
malformations.
5. Topo-isomerase inhibitors
a) Anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin, & mitoxantrone).
b) Plant alkaloids & natural products (taxanes), include (paclitaxel, docetaxel,
etoposide, vinblastine, & vincristine).
 Docetaxel  safe in the in 2nd & 3rd TM .
 Etoposide  no patterns of CFMF in later stages of pregnancy.
6. Molecularly targeted agents (tyrosine kinase inhibitor, imatinib & the
monoclonal antibody, rituximab)  mostly safe during 2nd & 3rd TM.15

16.  Chemotherapy is a contraindication to
breast feeding (except for Azathioprine).
 There is a concern with contact exposure of
healthcare workers to chemotherapeutic
agents.
 There is a 2-fold increased risk of foetal
loss in nurses exposed during 1st TM.
16

18. 18

19. Genital malignancy is
one of the most
encountered
malignancies during
pregnancy
19

20. 20
Cancer, fertility and pregnancy: ESMO Clinical Practice Guidelines for diagnosis,
treatment and follow-up (2010)

21. 21

22. 22

23.  The inc. of abnormal cx. cytology during
pregnancy is as high as that for non-
pregnant women.
 PAP smear can be performed during
pregnancy.
 Eversion of the endo-cx. during preg. 
exposure to vaginal acidity  higher
degree of sq. metaplasia , which is
important for HPV growth (which requires
active celluler growth to reproduce &
transform cells).
23

24.  Colposcopic examination during pregnancy is
easier due to eversion of the cx. & thus more
apparent TZ.
 However, must be performed by an
experienced colposcopist d.t. the following
limitations:
 High estrogen  hypertrophy & increased
vascularity  bluish hue  more aceto-white
areas
 Increased metaplasia  punctations & mosaicism
that  aceto-white areas,
 Cx mucus may  hinder colposcopic examination,
 Stromal oedema & decidualization (in the 2nd & 3rd
TM)may  suspicious appearance of the cx.
24

25.  Cx. biopsy could be taken, but more bleeding
is expected.
 Bleeding may be controlled by:
 Monsel solution,
 Silver nitrate,
 Vaginal packing, or even
 Suturing.
 Because false –ve colposcopy results are (8 -
40%) multiple random biopsies should be
avoided & only one “directed” biopsy is to be
taken.
 Endo-cx curettage should be avoided. 25

26.  Cx. Conizationis is better to be avoided as:
1.Excessive bleeding is common  bl. transfusion.
2.Risk of preterm birth is 1.6 folds higher.
3.Cx. epith., stroma & canal can’t be excised properly
(fear of abortion).
 Thus, unless invasive cancer is suspected or
identified, conization for Rx of CIN lesions (ante-
partum) is not recommended .
 Alternative to conization,
 Wedge resection of areas incompletely visualized
colposcopically.
 Shallow “coin” biopsy after haemostatic sutures.
26

27. 27
Application of 6 haemostatic
sutures , around the cx (close to
vaginal reflection):
 1) reduces B flow to the cone
bed,
 2) evert sq-col junction.

28.  ASCUS  as non-pregnant, (colposcopy
may be delayed to 6 ws postpartum).
 LSIL  colposcopy, (it can also be
delayed to 6 ws postpartum).
 HSIL  colposcopy & directed biopsy.
 AGC  colposcopy, (endo-cx. curettage is
better to be avoided).
 For adenocarcinoma in situ (AIS),
management = CIN 3 28

29. ASCUS
HPV testing
- ve
Cytology every 6 - 8
weeks
+ ve
colposcopy
29

30. 30

31. 31

32. 32

33.  Pregnancy impedes both staging & Rx.
 Induration of the base of the broad lig. is less
prominent during preg. (d.t. cx., para-cx. &
parametrial softening)  under staging.
 CT is of limited use during pregnancy. However,
MRI is useful in detecting spread.
 Cystoscpy & sigmoidoscopy can be also
performed.
33

34.  Rx depends upon
1. - stage of the disease,
2. - duration of pregnancy, &
3. - desire of the patient to continue pregnancy.
 Rx. of micro-invasive disease diagnosed by
cone biopsy follows guidelines similar to those
for CIN.
 In general, continuation of pregnancy & vaginal
delivery are safe.
 Definitive therapy is reserved until postpartum.34

35.  Invasive cancer demands prompt therapy.
 During the 1st half of pregnancy,
immediate treatment is advisable
(depending on the decision to continue
pregnancy).
 During the 2nd half of pregnancy, ((one
option)) is to wait not only foetal viability
but also foetal maturity.
35

36.  For stage I & early stage IIA lesions [< 3 cm ]  
radical hysterectomy + pelvic lymphadenectomy.
 Radical surgery is preferred to irradiation
(although cure rates are similar between both),
because it preserves ovarian & sexual function. In
addition, it avoids intestinal & urinary tracts’
exposure to radiation & its adverse effects.
 Before 20 weeks, hysterectomy en toto (with baby
in utero). While afterwards, hysterotomy is
performed first. 36

37. 37

38. 38

39. 39

40. Mostly, CIN with pregnancy will show regression
after delivery.
Mode of delivery:
 In pre-invasive cancer NVD could follow at term.
 For invasive cancer, C.S. is recommended, for
fear of cx lacerations & spread of the disease to
episiotomy site & vaginal lacerations.
 With CS, classical incision is preferred, as LUS
incision increases the risk of cutting through
tumour, which can cause significant blood loss.
Recurrence in the episiotomy scar was reported.
Prognosis is generally similar to non-pregnancy.
40

41. Rare due to age incidence !!!.
41

42. 42

43.  Most adnexal masses during pregnancy
are mature teratoma & cystadenoma.
 2 adnexal conditions are specific for
pregnancy:
• Pregnancy Luteoma.
• Theca-Leutin Cysts.
 Complications are more common during
pregnancy (as torsion or rupture).
43

44.  5% of adnexal masses in pregnancy are
malignant, compared to 15 -20% in non-
pregnants.
 Pregnancy does not alter the prognosis of
ovarian cancer.
 Most of ovarian cancers found during
pregnancy are common epithelial types,
then germ cell tumours.
44

45.  Problems during pregnancy is initial
diagnosis & differential diagnosis.
 Measuring tumour markers may be mis-
leading as α-FP, β-hCG, & CA125 are
elevated during pregnancy
 Rx of ovarian cancer in pregnant women
is similar to that for non-pregnants, but
with appropriate modifications
depending on gestational age.
45

46. 46
Adnexalmass(asymptomatic)
Repeat
US at
16-18
wk
Persistent
mass
Symptomatic
Laparoscopic
evaluation
(18-22 wks)
Suspicious
features:
** ↑ > 30% size
** Solid
components
** Excrescence
** Ascites
** ↑ low Resis
vascularity
Asymptomatic +
not suspicious
FU + post
partum
evaluation
Resolution

47. 47
Laparoscopic evaluation (18-22 wks)
BENIGN
Cystectomy
MALIGNANT, or
BORDERLINE
Adnexectomy
(if clinically early stage)
Chemo-Rx (if indicated)
at 34-36 ws
Postpartum Rx
** Metastatic work-up
** Continue chemoRx
** +/- completion surgery
Hands off the
uterus
whenever possible

48. 48
Recommendations for Laparoscopy in pregnancy
• 16 -12 weeks gestational age.
• Tilting table to the Rt or Lt.
• Lt upper quadrant (Palmer’s) or sub-xyphoid insertion (6 cm
between entry point & uterine fundus)
• Open Hasson technique is preffered
• If Veress technique is used, use u/s guidance with abdominal
wall elevation
• Intra-abdominal pressure 15 mmHg
• Trendelenberg position
• Contineous foetal monitoring

49. 49

50.  Pregnancy-Associated Breast Cancer
(PABC) =
Breast cancer diagnosed during pregnancy
or lactation up to 12 months post-partum.
 PABC is challenging, as
• Breast cancer is not screened in pregnancy.
• Diagnosis is difficult & usually delayed.
• All lines of Rx may affect pregnancy.
• Pregnancy hormones may influence of `disease.
50

51.  Breast cancer is one of the most
common malignancies encountered
during pregnancy & lactation.
 Incidence ranges from 1 : 3000 - 5000
pregnancies .
 The frequency of PABC is increased, as
more women choose to delay
childbearing until a later age.
 Pregnancy is not an independent risk
factor for cancer breast.
51

52.  The effects of pregnancy on the course &
prognosis of breast cancer are complex (↑↑↑ E –
the 3 tyes- & P levels):
 It is suggested that higher E levels during preg. 
excess breast cancer later in life,
& that P may be protective.
 Higher serum levels of alpha-fetoprotein are ass.
with decreased incidence of breast cancer,
therefore, pregnancy interruption following
diagnosis of pregnancy-associated cancer has no
influence on its course or prognosis.
52

53.  When breast cancer is diagnosed during
pregnancy, the regional LNs are more likely
to contain microscopic metastases.
 60% of pregnant women with PABC have
concomitant axillary node involvement.
 About :
 30% of pregnant ♀ with breast ca. have stage I
disease,
 30% have stage II disease, &
 40 % stages III or IV disease.
53

54.  Survival rate in women with PABC is (15-
20%) compared to (60%) in non-
pregnants.
 Advanced stage at diagnosis is due to:
• Breast engorgement  obscures the lesion.
• High pregnancy hormones (E2&P4)
• Increased vascularity & lymph drainage  more
metastases.
54

55.  Use of tamoxifen during pregnancy is
contraindicated (at any time) during
pregnancy as it  foetal malformation.
 Lactation after breast cancer , is usually
discouraged , for fear of vascular
engorgement of the other breast which
may contain a neoplasm.
55

56. 56

57. 57

59. In females:
 Surgical removal of reproductive tract.
 Surgical oophorectomy.
In males:
 Orchidectomy
 Surgical Rx in cancer bladder, prostate,
& rectum  interferes with sexual act
(potency & ejaculation).
59

60. Significant effects on fertility depends upon:
 Radical vs adjuvent chemo-Rx.
 Single vs combination chemo-Rx.
 Dose-dependent effect & cumulative effect.
 Drug-dependent effect.
 Age dependent effect.
(ovarian function is greatly affected after 40 ys- due to
decreased ov. reserve & higher oocyte attrition rates).
 Male vs female physiology.
(testicles are more sensitive to chemo-Rx).
60

61.  Cell cycle non-specific agents as
Cyclophosphamide (alkylating agents)
 destroy resting primordial cells.
 Cell cycle specific agents as
methotraxate (anti-metabolite agents)
 spare the resting primordial cells 
i.e. less toxic.
61

62. Agent Known Effect On Testis
o Cyclophosphamide Severe
o Nitrogen Mustered Severe
o Procarbazine Severe
o Bleomycin Moderate
o Carboplatin Moderate
o Cisplatin Moderate
o Doxorubicin Moderate
o Etoposide Moderate
o Ifosfamide Moderate
o Thioguanine Moderate
o Vinblastine Moderate
o Vincristine Moderate
o Methotraxate Minimal
62

63.  It destroys DNA  disturbing cell-cycle 
apoptosis.
 Unlike malignant cells, most of normal
cells have the ability to recover from the
effect of Radio-Rx.
 Depends on :
• Dose.
• Field (consider the effect of scattered irradiation).
63

64.  Ovarian irradiation may affect fertility &
hormonal function:
 A dose of 14.3 Gray, in ♀ > 30 years 
irreversible infertility & menopause
 While a dose of 6 Gray, in ♀ < 30 years 
reversible.
Ovarian
irradiation
64

65.  Uterus is relatively resistant to Radio-Rx.
 Radio-Rx may  ↓ ut. volume & ↓ bl. flow.
 Thus, may 
 Poor implantation,
 Mid TM abortion,
 PTL, &
 IUGR.
Uterine
irradiation
65

66.  Vagina is relatively resistant to Radio-Rx.
 Radio-Rx may  vaginal stenosis & loss
of lubrication.
 Thus, may 
 Physical impairment of sexual act, &
 Psycho-sexual disturbances.
Vaginal
irradiation
66

67.  3.5 Gray  reversible sterility (in 18-24 ms).
 6 Gray  irreversible Azoospermia.
 Effect depends on :
 Age (younger is better).
 Pre-Rx semen.
 Leydig cells are radio-resistant. Thus,
Testosterone production is less affected.
 Vascular affection may  erectile dysfun.
 Libido is not affected by Radio-Rx.
67

68. Fertility
Preservation
68

69. 1. Sterilizing cancer Rx.
2. Chemo-Rx for non-cancer disorders:
i. Lupus nephritis.
ii. Behcet’s disease.
iii. Bone marrow transplantation for Sickle Cell Anaemia.
3. Oophorectomy for:
i. Benign ovarian growth.
ii. Large endometriomas.
4. Family history of premature ov. Failure.
5. (?) Turner’s syndrome.
69

70. 70

71. 1. Hormonal Suppression of the Ovaries (GnRH-a).
2. Embryo cryo-preservation. (require 10-14 ds stimulation).
3. Oocytes cryo-preservation
a) Mature oocytes: require 10-14 ds of stimulation ICSI or freezing.
b) Immature oocytes : without stimulation  IVM +/- ICSI.
- Oocytes are more sensitive to cryo-preservation than embryos,
(d.t. Spindle damage from ice crystal formation).
4. Ovarian tissue cryo-preservation. ( transplantation,
or aspiration of imm. Oocyts, or isolation of primordial foll).
- The only method for children, & if there is no enough time for OI.
- Expensive & still experimental,
- Not suitable if there is high risk of ov. Involvement.
71

72. 72

73. 73

74. 74

75. 75

76. 76

77. Transplantation
of ovarian
tissue into
peritoneal
cavity
77

78. 78

79. 79

80. 5. Ovarian Transposition (oophoropexy).
 It should be performed very close to the time of irradiation due to
the risk of re-migration of the ovaries.
 Scatter radiation & altered bl. supply, are main causes of failure.
 IVF is indicated, but oocyte retrieval is difficult.
6. Ovarian shielding.
7. Trachelectomy (may need IVF of ICSI to conceive).
 For stage 1A2-1B , 2 cm diam + < 10 mm depth, > 40 years.
 Recurrence = radical hyterectomy.
 Risk of Mid TM abortion, PTL, infertility (cx. abnormality)
8. Uni-lateral oophorectomy, or ovarian cystectomy.80

81. Ovarian Transposition
81

82. 82

83. 9. Progesterone Rx in early endometrial carcinoma.
10. Anti-VEGF.
11. Photo-dynamic –Rx.
12. Donor Oocyte & Surrogacy.
13. Adoption !! (not a fertility preservation).
14. Derivation of Oocytes from Embryonic Stem Cells
(semi cloning).
83

84. 84

85. 85

86. 1. Hormonal Suppression (with GnRH-a & antag).
2. Testicular Shielding (during Radio-Rx).
3. Sperm cryo-preservation
obtained through masturbation, testicular aspiration or extraction,
OR electro-ejaculation (under sedation).
4. Testicular tissue cryo-preservation, then
reimplantation or grafting .
- The only method for children.
86

88.  There is no increased risk of cancer recurrence in
♀ who become pregnant after cancer Rx.
 Majority (79%) of gynaecologic cancers are
diagnosed at post menopause, thus fertility
preservation & conception after cancer Rx was
not studied well in such cases.
 A case was reported in (Aug 2013) of a 25 years
female who had conservative Rx for simultaneous
early ovarian & endom. malignancy, & then had a
NVD after spontaneous pregnancy.
88

89.  Partners of ♂ who receives childhood cancer-Rx don’t
have adverse pregnancy outcomes. Only Rx with non-
alkylating chemo-Rx increases risk of LBW off springs.
 ♀ who receives childhood cancer-Rx (esp. pelvic irrad.)
have higher incidence of premature, LBW, & SGA babies.
 Receiving doxorubicin or daunorubicin increases the risk
of LBW, independently of pelvic irradiation.
 There is no differences in risks of CFMF, single-gene
defects, or cytogenic abnormalities in survivors of
childhood cancer, regardless of type of cancer Rx.
89

90.  It’s advised to delay pregnancy 2 to 3 years, (the
most critical observation period). Women who
conceive before this time, do not appear to have
diminished survival.
 Women who become pregnant after Rxed breast
cancer have birth outcomes similar to those
without cancer.
 Pregnancy after Rx for early-stage, oestrogen
receptor (ER) +ve breast cancer does not affect
the recurrence rate.
90

91.  No data suggest that lactation adversely affects
the course of breast cancer.
 Successful lactation is possible after
conservative surgery & radiation for breast
cancer, even from the treated side.
 Induction of ovulation following breast cancer is
better by aromatase inhibitors (as Letrozole) or
anti-oestrogens (as Tamoxifen), rather than GnH.
91

93. o Before  Risk of recurrence breast Ca.
o Recently  not associated with breast Ca or
other types of Ca. (huge chines study 2008).
o  risk of
o Endometrial cancer.
o Ovarian cancer.
o Colo-rectal cancer.
o Higher risk for thrombo-embolism.
o Useful for anemia Rx. 93

94.  No enough studies.
 Not advised for hormonally dependent
Ca. survivors.
 Have different effects on breast tissue
(proliferative , non-proliferative or
neutral), depending on dose, type, &
time.
94

95. o NO risk of recurrence of breast Ca.
o IUS is
o Suitable esp in tamoxifen Rx,
o Useful for anemia Rx.
o Does not suppress ovulation (mostly), but
blood level is detected.
o Unknown risk of TE.
95

96. 96