pregnancy associated breast cancer

1. PREGNANCY AND BREAST CANCER
PRESENTER: DR DEEPAK KUMAR
SENIOR RESIDENT
ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI
MODERATOR: DR RITESH KUMAR

2. DEFINITION
 Pregnancy-associated breast cancer (PABC) refers to breast cancer that is
diagnosed during pregnancy or within the first postpartum year.
Breast cancer during pregnancy* Jeanne A. Petrek M.D. https://doi.org/10.1002/cncr.2820741341

3. INTRODUCTION
 Breast cancer is one of the most common malignancies affecting
pregnancy
 The incidence is increasing as more women delay childbearing
 Breast cancer can be safely diagnosed, staged, and treated during
pregnancy while protecting the fetus and mother with excellent outcomes
for both

4. EPIDEMIOLOGY
 Accounts for 3% of total Ca breast in women
 Exact incidence- difficult to estimate
 Recorded incidence- 1:5000- 1:50,000 (Smith et al, 2003)
 Recent studies- Incidence is 1:3000 (Anderson Tm et al. 2009)
 Incidence does increase with age, and the majority of women who
are diagnosed with PABC are 32-38 years of age
 Causes of increased incidence
1. Child bearing at late age
2. Life style changes
Wallack MK, Wolf JA Jr, Bedwinek J, Denes AE, Glasgow G, Kumar B,et al. Gestational carcinoma of the female breast. Curr Probl Cancer
1983;7:1-58.

5. MANY QUESTIONS???
 Ethical issues in best management of the mother and fetus
 Effect of cancer on pregnancy
– Effect of the tumor
– Effect of management
Effect on the outcome of pregnancy, special care, mode of delivery,
and fertility
 Effect of pregnancy on cancer
– Effect on biology
– Effect on management
Diagnosis : manifestations and diagnostic methods
treatment

6. EFFECT OF PREGNANCY ON
BREAST CANCER
 Not simply explained by high dose of estrogen
 Increased AFP and hCG are protective
 PABC are more likely to be advanced/ metastatic
(due to increased blood/ lymphatic supply)
 Microscopic lymph node involvement more likely in pregnancy (60%) (Ishida
T et al. 1992 , Middleton LP et al. 2003)
 Higher incidence of Inflammatory Cancers
 80% lesions are ER/PR negative (Loibl S et al 2005)
 Interruption of pregnancy does not alter the prognosis

7. DOES PREGNANCY AFFECT THE
PROGNOSIS?
 Slight delay in diagnosis- mean delay 1-2 months
 6 month delay increases chance of nodal involvement by 5% (TD-
130days) (Nettleton J et al. 1996)
 Post-pregnancy breast remodeling may favour tumour cell
dissemination
 Breast cancer is always more aggressive in young women (so
more common at advanced stage)

8. DELAY IN DIAGNOSIS

9. EFFECT OF BREAST CANCER ON
PREGNANCY
 Disease itself- very little effect, if any
 Adverse effects due to
1. Anesthetic drugs
2. Radiation
3. Chemotherapy
4. Hormonal agents
 Placental metastasis
Seen occasionally in inter-villus space
No transmission to the fetus due to
immune rejection by the trophoblasts

10. SIGNS & SYMPTOMS
 Painless mass or
breast skin thickening
 Breast feeding women
“ milk rejection sign”
 Increase breast weight

11. DIAGNOSIS AND STAGING OF
BREAST CANCER DURING
PREGNANCY

12. IMAGING
 Triple modality: clinical assessment, imaging, core biopsy
 Clinical assessment: Age, Clinical examination
 Ultrasound: Limitation due to dense breast due to pregnancy
 Initial screening
 No radiation exposure
 Distinguish solid Vs cystic lesion
2.

13. CHALLENGES IN TRIPLE
ASSESSMENT
 Normal physiological changes may
compromise
 Physical exam, make small masses
more difficult to detect
 Limited the utility of mammography
(sensitivity 86%)
 Limitations of imaging
 MMG: 0.04 cGy with fetal shielding,
(safe)
 MRI: Gadolinium crosses placenta)
(Cat C drug)
 Hesitation to proceed with tissue
diagnosis due to fear of fetal harm

14. METASTATIC WORKUP
Chest X-ray Should be done (fetal exposure 0.01 cGy)
Ultrasound whole abdomen Non invasive
Alkaline Phosphatase- Unreliable ( x2 or x4 during pregnancy)
CT scan abdomen Usually avoided (fetal exposure >2 cGy)
Bone scan Yield is low, selective use (fetal exposure0.4 cGy
MRI abdomen/ spine
Safer alternative, when indicated clinically

15. DOSE OF RADIATION BY IMAGING
Imaging modality Dose of radiation
Mammography 0.04 cGy
Bone scan 0.19 cGy
Low dose Bone scan 0.08 cGy
Chest radiograph 0.01cGy
Tc 99m scan 0.43 cGy

16. EFFECTS OF RADIATION EXPOSURE
TO FETUS
Weeks Of Gestation Dose Of Radiation
Abnormality Or
Malformations
< 8 weeks 10 rad (<0.1Gy) Microcephaly
Early pregnancy 50-200 rad (0.5-2 Gy)
Permanent growth
restriction
8-15 weeks 12-20 rad (0.12-0.2 Gy) Mental retardation
< 25 weeks >5-10 rad (0.05-0.1Gy)
Congenital
malformations
Negligible risk <1cGy

17. DIAGNOSIS (CONTD.)
Tissue Diagnosis
• If the mass is suspicious/ non-diagnostic
in imaging
• Lactation should be suppressed to
decrease vascularity and chance of milk-
fistula
• Needs expert pathologist
Normal
Pregnancy
Invasive
Cancer
Novotny DB, Maygarden SJ, Shermer RW, Frable WJ. Fine needle aspiration of benign and malignant breast masses associated with pregnancy. Acta Cytol 1991;
35: 676–86
FNAC Core biopsy
High rate of insufficient samples
Standard of diagnosis
Pregnancy induced changes
(lobular hyperplasia,
galactostasis)

18. Prevention: Milk Fistula
 Measures
 1. Stopping lactation 1 week prior to Bx
 2. Empty breast before Bx
 3. Bromocritine 2.5 mg BD or TDS
 Management: ice pack, breast binding
Assessment of Axilla
 ultrasound of axillar followed by FNAC if LN+
 Tc99m controversial
 Avoid blue dye – anaphylaxis reaction and unknown fetal effects

19. HISTOLOGY
 Similar to that of non-PABC
 More frequent receptor
negative tumor: due to high
steroid level

20. DIFFERENTIAL DIAGNOSIS
Associated with pregnancy
• May undergo H/P changes due to
hormonal stimulation
1. Fibroadenoma
2. Lipoma
3. Papilloma
4. Fibrocystic disease
Peculiar to pregnancy
1. Lactating adenoma
2. Galactocele
3. Mastitis
4. Breast abscess (Wall should be
biopsied)
Bloody nipple discharge
• Cytology is always
warranted
• Not a contraindication to
breast-feeding
1. Physiological
2. Infection
3. Duct papiloma
4. Carcinoma

21. THERAPEUTIC
MANAGEMENT

22. CHALLENGES IN TREATMENT
 Treatment should no be delayed due to pregnant state
 Rarity of the condition
 Lack of awareness in ladies as well gynecologists
 Communication gap b/w the health care providers
 Fear of harming the fetus: radiation, surgical stress,
chemotherapy
 Continuing the pregnancy

23. MANAGEMENT
• Multidisciplinary approach
1. Obstetricians
2. Surgeons
3. Neonatologists
4. Medical Oncologists
5. Anaesthetists
6. Psychiatric Counselors
• Respect patient’s wishes
• Individualized treatment: consider disease extent,
gestational age, impact on pregnancy, minimizing
harm to the fetus, and fertility planning

24. TREATMENT MODIFICATIONS
 Surgery is safe in all trimester
 BCS and ALND/?SLNB are viable options
 Chemotherapy should be avoided in first trimester
 Methotrexate & Trastuzumab: contraindicated
 Hormone therapy should be avoided till delivery
 Radiotherapy should be given after delivery
 If diagnosed post-partum- lactation to be suppressed and immediate treatment to
be started

25. MANAGEMENT OUTLINE
Time of diagnosis Surgical treatment Adjuvant Treatment
After delivery /post
partum
1st trimester
MRM (preferred)/ or
Lumpectomy with
axilla node dissection
2nd trimester adjuvant
chemotherapy
± Radiation
± Hormonal Therapy
2nd trimester / early 3rd
trimester
MRM (preferred)/ or
Lumpectomy with
axilla node dissection
± adjuvant
chemotherapy
± Radiation
± Hormonal Therapy
± adjuvant
chemotherapy
Late 3rd trimester
MRM / or Lumpectomy
with axilla node
dissection
Adjuvant
chemotherapy
± Radiation
± Hormonal Therapy

26. SURGERY
• Treatment of choice for non-metastatic disease
• Peri-operative hazards- Position, Anesthesia, Risk of preterm labour
• Modified radical mastectomy (MRM) with axillary clearance-
preferred in most cases
 Mastectomy and axillary dissection stage I-II – eliminate role of RT
 Axillary dissection preferred – chemo regimen decision
• Breast Conserving Surgery (BCT)
Lumpectomy/ Quadranectomy + Axillary Clearance
Needs adjuvant RT after delivery
Preferred for localized Tx diagnosed in 3rd trimester

27. PHYSIOLOGICAL CHANGES DURING
PREGNANCY
 Hypercoagulability
 Delayed gastric emptying
 Increase blood volume and cardiac output
 Decrease functional residual capacity of lung
 Decrease serum cholinesterase activity of lung
 Anesthetic needs
 Pre-oxygenation
 Antacid
 Anti thrombotic measures
 Rapid sequence induction with cricoid pressure
 Cushion under right hip to reduce vena cava compression

28. SENTINEL LN BIOPSY
 Debatable topic
 RISK OF SURGERY
 1. SPONTANEOUS ABORTION and Pre term labor (RR=1.58-2.0 )
SLND Axillary dissection
Fetal exposure 0.5 cGy No radiation exposure
Within Safe limits PABC – LN positive (2/3rd)
Insufficient data Chemoregimen determination
Miscarriage, LBW, congenital malformations
(few studies)
Combine with BCS in 3rd trimester
Double filter Tc99m sulfur colloid -500-
600µCi safe (Niklas and Baker et al 2000)
Isosulfan dye- unknown toxic effects

29. CHEMOTHERAPY
• Indications- Axillary LN +ve, growth >1 cm
• Category D drug

30. • Early pregnancy- Teratogenic (3-8 weeks of embryonic age) → needs
MTP
• Fetal malformation (Doll DC et al. 1989)
 1st trimester -14%-19%
 2nd trimester – 1.3%
• Late pregnancy- Can be given in late 2nd and 3rd trimester
 Administer without dose modification and dose as per body weight and
BSA
 With held chemotherapy at 35th week – avoid hematological nadir at
delivery
• Breast feeding should be avoided during chemo

31. SAFETY OF CHEMOTHERAPY
DURING PREGNANCY
Study No of patients Gestation period Malformations
Cardonick et al. (2010) 104 20.4±5.4
IUGR(8),
pulmonary(5),hyperbilirubinemia(2)
Death(1)
French national survey
(1999)
20 1st trimester (2) Spontaneous abortion (2)
Mir et al. (2008) 50
1st trimester (3)
2nd trimester (47)
Spontaneous abortion (2/3)
Fetal complication (3/47)
CAF (Cyclophophamide, Adriamycin, 5-FU) is the preferred regime
CMF-
Methotrexate (Mtx) instead of Adriamycin- Controversial
 Mtx can kill the trophoblasts

32.  Taxanes
 Data not strong
 Anthracyline based chemotherapy frequently initiated.
 Decrease effectiveness – upregulation of cytochrome P-450
Author No of patient Gestation Malformations
Mir et al. 2010
40 (21-pacli, 16-
doce, 3-both)
2/30/8
T1/T2/T3
Pyloric stenosis
(1)

33. Other Therapies
 Radiotherapy
Contraindicated- deferred till delivery
Maternal dose of 5000 cGy exposes the fetus to 100-150
cGy
Trimester Dose of radiation (if received)
1st trimester 0.039-0.15 Gy
2nd trimester 0.02-0.246 Gy
3rd trimester 0.02-0.586 Gy
0.1-0.9 Gy – mental retardation
0.05 Gy (5 cGy) relatively safe upper limit ( Brent et al.)
≥ 0.1Gy – therapeutic abortion should be considered ( Hall et al.)

34. • Immunotherapy
• Trastuzumab-Herceptin (monoclonal Ab
against HER2/neu)
• Limited experience in pregnancy (case reports)
• May cause oligohydramnios, anhydraminos,
renal dysfunction (Witzel ID et al. 2008)
• Hormonal therapy
 Tamoxifen is teratogenic (Cat D drug)
 Malformation- 20%
 Ambiguous genitalia (Cunha GR et al. 1987), Goldenher
syndrome
 Aromatase inhibitors- contraindicated
 Oophorectomy- little help
(Shrim et al, 2008; Sekar and Stone, 2007)

35. FETAL SURVEILLANCE IS MUST
Pre term delivery: Try for lung maturity
 USS for anatomic evaluation
 Growth scan every 4 weeks and Doppler USS if concern for
growth restriction
 Antepartum fetal testing at 32 weeks or sooner if growth
restriction noted
 Delivery at close to term as possible
 Send placenta for pathology
 Not an indication for caesarean section

36. FUTURE PREGNANCY
• No adverse effect on future obst outcome
• Most of the recurrence- within 2-3 years
• Better to plan next pregnancy after 2-3 years of
completion of therapy.
• Stage III – wait till 5 yrs
• Stage IV – discourage subsequent pregnancy
• Recurrent I-II: no future pregnancy
• Chemo may cause ovarian failure
• Survival is even BETTER! than those who don’t
conceive

37. LACTATION
 Lactation is contraindicated during chemotherapy.
 Formula feed- option
 Breast feeding- 3-4 weeks after last chemotherapy.
 Chemotherapy affects milk production – 55%
women can successfully feed (Cardonick et al.
2010)
 Radiotherapy also affects lactation- fibrosis
Mamma is on
chemotherapy

38. SUPPORTIVE MEDICINE
 Antiemetics ( ondansetron, granisetron)- cat B
drug
 Dexamethasone- nausea prophylaxis
 Nk-1 inhibitors- less studied- avoid
 G-CSF support- vital (neonatal neutropenia/
sepsis)
 Peg-filgrastim- less data

39. SURVIVAL & OUTCOME

40. PROGNOSIS
S Treiti et al. 1998
N=35;
(20-PABC; 15- lactating)
Ip, IIp=40,
IL,IIL=30
Median delay
 PABC-2.5mos
 Lactating-6mos

41. PABC
N=154
NON PABC
N=308
P VALUE
Median
delay
2.16 1.18 <0.001
RFS 0.69 0.81 <0.001
MFS 0.45 0.68 <0.001
5YR-OS 0.61 0.75 <0.001
Pascal BONNIER et al. 1997

42. Beth M. Beadle, et al. 2009
10yr PABC
N=104
NON PABC
N=564
LRR 23.4 19.2
DM 45 39
OS 64 64

43. OUTCOME
Hahn et al.
2006
10% reversible
breathing difficulties
N=57 1-SAH (recovered)
1-down syndrome
2-congenital
malformations
Cardonick et al.2010 8- <10% BW for
gestation
N=113 19- pregnancy
complication
3.8%- malformation
No significant difference Vs. general
population
Long term outcome
Aviles et al. 2001 Reynosos et al. 1987
N=84 N=8
No significant difference cardiac,
physical, neurological abnormality
1- multiple congenital abnormality,

44. MANAGEMENT ALGORITHM

45. Our experience (AIIMS,IRCH)
Incidence 0.7% (26/3750 cases)
Median age of diagnosis 20-35
Symptoms duration 11.5mos
Distribution Stage I-1, stage II-3, stage III-14,
stage IV-8
Median tumor size 5.5 cm
Diagnosis 1st trimester-2
2nd trimester- 2
3rd trimester- 3
Post partum- 19
ER/PR (-)
HER2/neu (+)
56%
38%
3- yr RFS
3-yr OS
40%
50%
Dr Ajay Gogia et al.
2014

46. SUMMARY
 Most common malignancies diagnosed during pregnancy
 Incidence is increasing as more women delay childbearing
 Pregnancy termination does not improves survival
 The index of suspicion must be high and avoid the delays in diagnosis and
treatment
 Breast cancer surgery can be performed safely during all trimesters and BCS
& ALND are not contraindicated
 Radiation is generally avoided until postpartum

47. SUMMARY
 Chemotherapy can be safely administered during the second and third
trimester
 Use of trastuzumab and endocrine therapy is avoided
 Retrospective studies have shown excellent short-term and long-term
outcomes in children
 Care should involve a multidisciplinary team to optimize outcomes for the
mother and fetus
 Data on outcomes are mixed: most studies show that prognosis of PABC is
equivalent to non-PAB provided that they receive prompt standard therapy.

48. MD Anderson protocol

51. THANKYOU