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Cancer in Pregnancy
Jeffrey L. Stern, M.D.
Physician Reaction
• Ob/Gyn: Oh No! She has cancer!
• Med Onc: Oh No! She’s pregnant!
• Surgeon/Primary Care: Oh No! She’s
pregnant and has cancer!
• Get a Gyn/Onc involved!
Incidence
• 1/1000 – 1/1500 term pregnancies
• Incidence increasing: delayed childbearing
Frequency by Cell Type
Frequency in Reproductive
Age Group
Breast Cancer
30%
Lymphoma
10%
Leukemia
23%
Melanoma
30%
Cervix
35%
Ovary
15%
Bone/soft tissue tumors
25%
Thyroid
50%
What’s Different About
Pregnancy?
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Hormones
Metabolic Changes
Hemodynamics
Immunology
Increased vascularity
Age
Few cases – anecdotal experience
Inherent bias – breast, ovarian cancer
General Considerations
• Pregnancy does not have a proven
negative effect on any cancer
• Maintaining pregnancy after diagnosis
– Delay of treatment (assume delivery at 34th week)
• First trimester diagnosis: up to 28 week delay
• Second trimester diagnosis: up to 22 week delay
• Third trimester diagnosis: up to 10 week delay
General Considerations
• Surgery
– Wait until 16-18 weeks for abdominal surgery:
Spontaneous Abortion: 40%  3%
– Don’t remove corpus luteum if possible until
14th week (progesterone supp. 50mg BID)
– Deliver at maturity (at around 34 weeks)
– No proven teratogenic effects of anesthesia
General Considerations
• Chemotherapy
– First trimester (organogenesis ends at 12th week)
• Increase incidence of anomalies and abortion; drug
dependent i.e. antimetabolites (MTX)
• IUGR and preterm labor are common
– Second and Third trimester
• Delay chemotherapy if possible until 16th week
– end of the rapid growth phase
• No increase in incidence of abortion
• IUGR and preterm labor are common
• Delay chemotherapy if possible until 16th week
– end of the rapid growth phase
General Considerations
– Chemotherapy and Breastfeeding
• Generally not recommended
– Long-term effects of chemotherapy on children
exposed in utero
• Aviles, et.al. 43 cases with f/u for 3-19 yrs.
Normal: Physically
Neurologically
Intelligence
Psychologically
Sexual Development
Hemotologically
Bone Marrow Cytogenics
General Considerations
• Radiation Exposure
– Diagnostic Radiation
• Avoid “unnecessary” diagnostic
pelvic x-rays
• Use MRI when possible
• CXR/Mammogram – little risk
with shielding
– Therapeutic Radiation
• High incidence of abortion and
anomalies
-Dose and trimester dependent
Dose to Fetus
KUB
200 millicentigray
B.E.
450-900
CXR
1
CT Scan
900
IVP
600
L/S Scan
275-725
Lung Scan
370
Pelvic X-ray
210
UGI Series
170-330
General Considerations
• Obstetrical Considerations
– First trimester SONO: if dates?
– Level 2 SONO at 20 weeks
– Chromosome analysis
• Amnio: 15 weeks
• CVS: Transcervical (except cervix ca)
or transabdominal at 10-12 weeks
– Deliver when mature
• L/S ratio at 34 weeks
• Betamethasone
Epidemiology of Genital
HPV/SIL/Cancer in Pregnancy
• Up to 40% of reproductive age women have HPV
• 2.0-6.5% cases of CIN/SIL occur in pregnant women
• 13,500 cases of cervical cancer & 4,000 deaths/ year
in U.S.
• 25% of women with cervical cancer are < 36 years old
• 1-13 cases of cervical cancer for every 10,000
pregnancy
• 1.9% of microinvasive cervical ca. occurs in pregnancy
• Stage for stage – prognosis is not effected by
pregnancy
Screening for Cervical
Cancer/SIL
• Symptoms of cancer similar to physiologic
changes of pregnancy
• Often a delay in diagnosis (fear of biopsies)
• Pap smear at registration and 8 weeks postpartum
– Ectocervical scrape
– Endocervical swab / brush – risky
– Reflex HPV typing
• Pap less accurate in pregnancy:
– increased false negative rate
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Blood, inflammation
Failure to sample SCJ
Concern about bleeding
Difficult to see cervix: put CONDOM over speculum
Absence of endocervical cells
Absence of Endocervical Cells
Conventional PAP Liquid PAP
Non-pregnant
20%
10%
Pregnant
40%
20%
Post partum
30%
15%
Post menopause
70%
35%
Diagnosis of SIL and Cervical
Cancer
• Careful palpation of cervix: no induration or enlargement
• Biopsy all suspicious lesions: even if Pap/HPV are neg.
• Abnormal Pap:
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ASCUS/LSIL and HPV negative – repeat post partum
ASCUS/LSIL and HPV positive: colposcopy
ASCH: Colposcopy
HSIL: Colposcopy
• Don’t defer biopsy because of fear of bleeding or
preterm labor. First trimester easiest.
• Control bleeding with:
– Pressure, Monsell’s solution (Ferric subsulfate), Silver nitrate
Management of Cervical SIL On
Biopsy
• Satisfactory Colposcopy
– LSIL / HPV+/- :
• Re-evaluate 6-8 weeks postpartum
• 50% regress postpartum: delivery route seems
to matter
– HSIL / HPV+/- :
• Follow up depends on trimester
• 30% regress postpartum
• Vaginal delivery OK
Management of Cervical SIL
• Cone biopsy in pregnancy
– Indications
• Unsatisfactory colposcopy/ Pap: SCC
• Adenocarcinoma in situ
• Microinvasive SCC
– Perform at 16-18 weeks
– Risks
• Abortion: 5%
• Hermorrhage: immediate: 9%, delayed: 4%
– Technique
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Local wedge resection
Shallow cone
LEEP
Circumferential figure 8 sutures at cervical-vaginal junction
Vasopressin/ local anesthetic with epinephrine
Management of Cervical SIL
HSIL/ HPV positive: No Lesion Visible on
Colposcopy
– Reinspect: Vulva, Vagina, Anus and Cervix
– Lugol’s: Vagina and Cervix
– Review Cytology
– Consider Random Biopsies: 6 and 12:00
– Careful Follow-up: Pap and Colpo
Vulvar/ Vaginal Condylomata or SIL
in Pregnancy
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Warts and SIL often enlarge rapidly in pregnancy
No treatment unless symptomatic
Often regresses dramatically postpartum
Treat if symptomatic or interferes with vaginal delivery disease on perineal body or posterior fourchette
• Treatment options:
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Trichloroacetic Acid
Podophyllin
Aldara
5-FU cream
Laser
Excision: scalpel; LEEP
Cryotherapy
Cervical Cancer in Pregnancy
• Work-up
– MRI of pelvis/abdomen
– Chest X-ray
– Carcinoembryonic Antigen (CEA)
– CBC, BUN, Creatine, LFT’s
• Advanced disease
– Urine cytology/ cystoscopy
– Stool for occult blood/ sigmoidoscopy
Cervical Cancer in Pregnancy:
Treatment by Stage
• Stage IA1 - <3mm invasion; < 7mm wide
– 1.2% positive nodes
– Cone biopsy: no further treatment necessary
– Vaginal delivery at term
– Simple hysterectomy post-partum or Cesarian
hysterectomy at term
Cervical Cancer in Pregnancy:
Treatment by Stage
• Stage IA2 (3-5mm invasion, no vascular inv.):
– 6.3% positive nodes
• Stage IB – Disease confined to cervix
• Stage IIA – vaginal extension
– Vaginal delivery: increased risk of hemorrhage and
cervical laceration
– Depends on desire for pregnancy
• First trimester: delay of up to 28 weeks – degree of risk
unknown
• Radical hyst. and pelvic LND at diagnosis
• “Radical” cone biopsy/ trachelectomy/ cerclage and
extraperitoneal pelvic and aortic LND at 16-18 weeks
• C-Section and Radical hyst. and pelvic LND when mature
Cervical Cancer in Pregnancy:
Treatment by Stage
• Stage IA2, IB, IIA
– Second trimester: delay of up to 22 weeks
• Depends on desire for pregnancy
– Can probably safely wait until maturity
– Third trimester: delay of up to 10 weeks
• C-section, Radical hysterectomy and pelvic
Lymph node dissection at maturity
Cervical Cancer in Pregnancy: Treatment
by Stage
• Stage IB (bulky) or Stages IIb-IV
– First trimester – delay of up to 28 weeks
• Depends on desire for pregnancy
– Unwanted
» Whole pelvic radiation therapy/ chemotherapy
» If SAB occurs before XRT is finished – proceed with
cesium insertions (about 35 days)
» Occasionally will need hysterotomy and pelvic LND if
no SAB and then cesium insertions; or a “small” radical
hyst. & pelvic LND if small residual cervical disease
– Wanted
» Consider chemotherapy until maturity at 34 weeks
Cervical Cancer in Pregnancy:
Treatment by Stage
• Stage IB (bulky) or Stages IIb-IV
– Second trimester – delay of up to 22 weeks
• Unwanted: pregnancy – Radiation therapy as above
– Spontaneous abortion at 35 days
• Wanted: pregnancy – consider chemotherapy until maturity
– Third trimester – delay of up to 10 weeks
• C-Section at maturity/ staging lap; transpose ovaries
• Start radiation therapy 2 weeks postpartum
• Consider chemotherapy until maturity
Juvenile Laryngeal HPV
• 3.5 million deliveries in U.S./year
• Prevalence of HPV: 10-40%
• Infected pregnant women: 350k - 1.5
million
• 120 cases annually
• Risk to infant (1:2,900 – 1:12,500)
• VAGINAL DELIVERY
Ovarian Masses in Pregancy
• Overall incidence
– 1:500 pregnancies
– Increased incidence secondary to sonography
• Incidence of true neoplasms
– 1:1,000 pregancies
• Incidence of ovarian cancer
– 1:10,000 – 1:25,000 pregancies
• Unexpected adnexal mass at C-Section
– 1:700 pregnancies
Ovarian Masses in Pregnancy
Frequency by Type
• Non-neoplastic – 33%
– Corpus luteum cyst
– Follicular cyst
• Neoplastic – Benign – 63%
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Dermoid (36%)
Serous cystadenoma (17%)
Mucinous cystadenoma (8%)
Others (2%)
• Neoplastic – Malignant – 5%
– Low malignant potential (3%)
– Adenocarcinoma (1%)
– Germ cell / Stromal tumor (1%)
Management of Ovarian Masses in
Pregnancy
• Generalizations
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Symptoms
Ultrasound/ MRI appearance
Size
Gestational age
Tumor markers
• B-HCG, AFP, CA-125 all increased in pregnancy
• CA-125 should be normal after 1st trimester
– Fear of missing cancer or development of
complications
• Corpus luteum resolves by 14th week
• Ovarian cysts “benign” by Ultrasound or MRI, < 6 cm,
that do not change over time, do not require surgery
• Cysts greater than 6-8 cm or inc. in size: “usually” operated on
• Cysts which persist after 18th week are “usually” operated on
– Usually operate at 18 weeks to minimize fetal loss
Complications of Ovarian Masses in
Pregnancy: 10% Total
• Severe pain: 25%
• Obstruction of labor: 15% – C-Section
• Torsion: 10% of cases
– Sudden pain, Nausea & Vomiting etc.
– Most common at:
• 8-16 week – rapid uterine growth (60%)
• Postpartum – involution (40%)
• Hemorrhage: 10% of cases
– Ruptured corpus luteum
– Germ cell tumor
Complications of Ovarian
Masses in Pregnancy
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Rupture/ tumor dissemination (10%)
Anemia
Malpresentations
Necrosis
Infection
Ascites
Masculinization of female fetus
– Hilar cell tumor
– Luteoma of pregnancy
– Sertoli-Leydig cell tumor
Work-up of Ovarian Cancer
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Pelvic ultrasound
MRI pelvis/ abdomen
Chest X-ray
CA-125: elevated in normal pregnancy, should
normalize after 12 weeks
• AFP, B-HCG, LDH – predominantly solid mass
• Liver FunctionTests, BUN, Creatinine
• GI studies only if clinically indicated
Management of Ovarian
Cancer
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Prognosis not affected by pregnancy
Tumors of Low Malignant Potential – all stages (20%)
Adenocarcinoma Stage I, grade 1 or 2 (10%)
Germ cell tumors (5%) – may require chemotherapy
Gonadal stromal tumors (15%)
Surgery at 16-18 weeks if possible
Frozen section: beware of inaccuracies
Conservative ovarian surgery
– Adnexectomy/ Oophorectomy/ Cystectomy
• Hysterectomy not indicated
• Thorough staging:
– Pelvic/ aortic node disection/ Omentectomy/ peritoneal biopsies
Management of Ovarian
Cancer
• Epithelial Ovarian Cancer Stage IC – IV
– Try to delay chemotherapy until 12-16 weeks of
pregnancy
– Try to delay removal of corpus luteum until 14 weeks
– First trimester
• TAB followed by appropriate surgery and chemotherapy
• Chemotherapy after FNA:
– C-Section and appropriate management at maturity
– Second and Third Trimester
• Chemotherapy first
– C-Section and appropriate surgical management at maturity
Malignant Germ Cell Tumors
• Dysgerminoma
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30% of Ovarian malignant neoplasms in pregnancy
Most stage IA
Average 25cm; solid
Therapy
• Surgery: USO, wedge biopsy of opposite ovary, surgically stage
– 25% are bilateral
• Stage IA & IB: No further treatment
• Advance stages
– Hysterectomy not required
– Chemotherapy
Malignant Germ Cell Tumors
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Endodermal sinus tumor
Grade 2-3 malignant teratoma
Choriocarcinoma (non-gestational)
USO and staging for early disease
All require chemotherapy regardless of
stage
Tumor like Ovarian Lesions
Associated with Pregnancy
• All resolve spontaneously after delivery
• Conservative surgical approach: frozen section +/oophorectomy
– Luteoma of pregnancy - usually an incident. finding at C-Section
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Microscopic. -20cm – multiple nodules
Bilateral: 1/3 of cases
25% have increased. testosterone
Maternal masculinization. – later ½ of pregnancy
Fetal virilization – 70% of female infants
Hyperreactio Luteinalis - Bilateral multicystic theca lutein cysts
Large solitary luteinized follicular cyst of pregnancy
Hilar Cell Hyperplasia – masculinized fetus
Intrafollicular Granulosa cell proliferations
Ectopic Decidua
Breast Cancer in Pregnancy
(2nd most common cancer in pregnancy)
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20% of cases are in women <40 years old
1-2% of cases are pregnant at time of diagnosis
One case/1500-3000 pregnancies
Often difficult to diagnose
Low dose mammogram with appropriate shielding of
fetus is “safe”
MRI – probably best
Diagnosis often delayed
Increase incidence of positive nodes (80%)
Termination of pregnancy & proph. castration is not
beneficial
No adverse effects on prognosis from subsequent
pregnancies
Treatment of Breast Cancer
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Treatment same as non-pregnant
Lumpectomy
Sentinal node biopsy
– 2.5mCi technetium 99 – 4.3 mGy at worst. Usually contraindicated.
– +/- radiation
– Chemotherapy
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Modified radical mastectomy and nodes
Adjuvant chemotherapy after 16 weeks
– CAF better than CMF in 1st trimester
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Axillary or localized chest wall RXT is probably safe after the first
trimester but can be difficult to shield fetus.
Prognosis:
5 Yr Disease Free
Survival
Stage I
85%
Stage II
60%
Stage II
40%
Stage IV
5%
Leukemia in Pregnancy
• Most abort spontaneously
• Average age is 28
• Usually recommend termination of
pregnancy because of aggressive
chemotherapy
• Prognosis – dependant on cell type
5 Yr Disease Free
Survival
AML
10%
ALL
40-60%
CML
50%
CLL
Excellent
Hodgkins Disease/Lymphoma in
Pregnancy
• Gestational Age/ Stage
– <20 weeks: TAB
– >20 weeks: XRT
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Chest mantle first
Chemotherapy depending on stage
Abdominal XRT after delivery
80% curable – depending on cell type
Melanoma in Pregnancy
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Incidence rising
30% occur in women of child bearing age
9% of cases occur in pregnancy
Extremities most common site
Pregnancy does not affect prognosis
Ovarian Function and
Chemotherapy
• Dose and age related
– Younger than 25: permanent amenorrhea uncommon
– Older than 40: 50% permanent ovarian failure
• Birth control pills may prevent ovarian failure
• Risk of birth defects in offspring not increased (4%)
• Wait 2-3 years after therapy to become pregnant
– Allow for possible recurrent disease
Ovarian Function and Fertility
and Radiation Therapy
• Age and dose related (<20 years old – better)
– Ovaries outside radiation field (avg. dose 54 cGy):
• No failure
– Ovaries at edge of radiation field (avg. dose 290 cGy):
• 25% failure
• Start to lose function at 150 cGy
– Ovaries in radiation field:
• At 500 cGy most women are amenorrheic
• Oophoropexy to the iliac fossa
– Use clips to identify ovaries
Metastases to Fetus/Placenta
• Only 50 cases in literature
• Melanoma (50% of reported cases)
• Leukemia: 1/100 affected
pregnancies
• Lymphoma
• Breast
Reference List
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Barber H.R.K., Brunschwig A: Am. J. OB/GYN, 85.156, 1963.
Baltzer J., Regenfrecht M., Kopche W., Carcinoma of the Cervix
and Pregnancy Int. J. Gyneco Obstet. 31:317, 1990.
Zemlickis D., Lishner M. Degendorfer P.et.el. Maternal and fetal
outcome after breast cancer pregnancy. Am.J. Obstet. Gynecol.
9: 1956, 1991.
Karlen J.R. et.al. Dysgermenoma associated with pregnancy.
OB/GYN 53:330, 1979.
P.Struyk, P.S. Ovarian Masses in Pregnancy Acta.Scand. 63:
421, 1984.
Aviles, A. et.al. Growth and Development of Children of Mothers
Treated with Chemotherapy during pregnancy: Current status of
43 children. Am. J. Hematology 36: 243, 1991.
Brodsky et.al. Am. J. Obstet, Gynecol. 138:1165, 1980.