Transcript 1414724637_3101

Case report:
Adjuvant chemotherapy for
pregnant breast cancer patients.
(PABC; pregnancy-associated breast cancer).
2014/10/13
張嘉顯
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Patient information: (2014/10/10 OPD)
37 y/o, married F, BH:160.6 cm, BW: 56 kg
C.C.
Discuss with doctor for further breast cancer treatment.
Underlying
disease
 Breast cancer:
 T1N1M0, ER(-), PR(-), HER2(+).
 s/p pregnancy termination.(Gestational age(GA):12 wks).
 s/p MRM. (2014/9/17).
 Gastric ulcer:
 Gastric ulcer without HP infection by panendoscope s/p
treatment at Jen-Ai hospital.
Renal
function
(2014/9/10)
BUN(mg/dL)
Ccr(mL/min)
8
98.6
Scr(mg/dL)
eGFR(mL/min/1.73^2)
0.69
102
Liver
Function
(2014/9/10)
T-bilirubin
0.34
AST (U/L)
13
(mg/dl)
ALT(U/L)
7
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History of present illness:
 visited Jen-Ai Hospital for help.
 Core biopsy revealed an
invasive ductal carcinoma.
 Modified radical mastectomy.
 Set port-A.
 Pregnancy termination.
(pregnacy for12 wks)
Found
bloody nipple
discharge on
right breast.
And also
found she
had pregnacy.
Early
2014/8
 Visited KFSYCC.
 Examination revealed
infiltration ductal carcinoma
(NG3,ER0,PR0, HER +++)
2014/8/25
 KSFYSCC OPD follow-up.
 Arrange the further treatment.
2014/9/9
2014/9/17
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Patient information: (2014/10/10 OPD)
37 y/o, F, BH:160.6 cm, BW: 56 kg
ALL Hx
Nil
Current medications/
GYN Hx




Operation Hx
 C/S x 2 in USA.
Social Hx
 Smoking (-)
 Alcohol consumption: (-)
 Betel nut chewing: (-)
Family Hx
 Mother died of colon
cancer.
G4 P2 A2.
Menarche: 14 years old.
LMP:2014/07.
Breasting feeding.
 Gastric ulcer medication from JenAi Hospital (need to check the item).
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Problem list
Breast cancer.
Gastric ulcer.
If the patient were not performed pregnant termination…
How to perform the further treatment
for the pregnant breast cancer patient?
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Goal
 Cure or palliative ?
 To Cure the patient is our goal.
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PABC
 Definition of PABC :
Breast cancer is diagnosed
 during pregnancy.
 in the first postpartum year.
 any time during lactation.
 The most common malignancy occuring
pregnancy.
 Incidence rate: 1 in 3000 pregnancise.
EUROPEAN JOURNAL OF CANCER 46(2020)3158-3168.
UPTODATE: Gestitional breast cancer: Treatment. 2014.
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PABC vs non-PABC
 Compared PABC with non-PABC:
 For PABC in the first postpartum:
Death risk : PABC > non-PABC.
 For PABC during pregnancy:
OS, DFS : PABC ≒ non-PABC.
UPTODATE: Gestitional breast cancer: Treatment. 2014.
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Treatment principles for PABC:
 Treatments for PABC are generally the same as nonPABC, but they need some modification to protect fetus.
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Treatment principles for PABC:
 Local treatment.
 Systemic treatment:
 Timing.
 Regimen.
 Supportive treatment.
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Local treatment for PABC:
 Local treatment:
 The local treatment available for the non-PABC
patients can also be performed for the PABC patients,
ex. Mastectomy.
 Exception: Radiation therapy.
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Systemic treatment for PABC:
 Timing of treatment about delay chemotherapy:
 Decrease disease-free survival.
 Increase risk of metastasis.
(↑5-10 %Delay chemotherapy for 3-6 months).
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Systemic treatment for PABC:
 Timing of treatment about trimester
General concepts about pregnancy:
- Gestational age: last normal menstrual period
(LMP) to the time during pregnancy.
- Full term pregnancy: Gestational age ≥ 37 wks.
- Pregnancy consists of 3 trimesters:
1st trimester: 0-13 wks.
 The 2nd trimester: 14-26 wks.
 The 3rd trimester: 27-40 wks.
 The
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Systemic treatment for PABC:
 Timing of treatment (head?) :
The 1st trimester:
0-13 wks.
The 2nd trimester:
14-26 wks.
The 3rd trimester:
27-40 wks.
The important
organogenesis
period.
More vulnerable to
chemotherapy.
Less vulnerable to
chemotherapy.
It is recommended to begin chemotherapy after the 13th wks.
EUROPEAN JOURNAL OF CANCER 46(2020)3158-3168.
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Systemic treatment for PABC:
 Timing of treatment (tail?):
To allow the bone marrow to recover and to
minimise the risk of maternal and fetal neutropenia

Delivery should be planned 3 wks after the last
chemotherapy.
(Stop chemotherapy about at the 35th wk).
EUROPEAN JOURNAL OF CANCER 46(2020)3158-3168.
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Summary : Timing for treatment:
 For PABC patient, delayed chemotherapy can:
Decrease disease-free survival.
Increase risk of metastasis. (↑5-10 %).
 The suitable period for taking chemotherapy:
The 2nd and 3rd trimester. (about 14-35 wk).
To reduce the interference for oganogenesis.
To reduce the risk of myelosuppression at birth.
EUROPEAN JOURNAL OF CANCER 46(2020)3158-3168.
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FAC/AC regimen for PABC:
 A most common regimens in PABC now.
(with more sufficient data compared with other regimens).
 A prospective single-arm study (Cancer 2006; 107:1219).
(other smaller retrospective anthracycline-based chemotherapy have similar findings.):
Subjects
Regimens and timing
Efficacy outcomes(Follow-up:38.5 months)
57 PABC
patient
without
metastasis.
 During 2nd ,3rd trimester
 Free of disease and alive:40 pts.
(14-35 wks).
 Had recurrent breast cancer: 3 pts.
 FAC regimen:
 Death: 13 pts (12 pts for mets, 1 pts for PE.)
(F) 5-FU
500 mg/m2 IVB on D1, D4.
(A) Doxorubicin:
50 mg/m2 cIF over 72 hrs.
(C) Cyclophosphamide
500 mg/m2 IV on D1.
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FAC/AC regimen for PABC:
 Safety outcome (Cancer 2006; 107:1219):
 No stillbirth/miscarriage.
 The majority of the children didn’t have any significant
neonatal complications and seem to be similar to reported
norms for the general population.
 Caution: no long-term safety data. (Follow-up:2-152 months)
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Taxane regimen for PABC:
 Compared with FAC/AC, the taxane regimens are less
sufficient data.
 2010 systematic review of 40 case reports of taxane
administration during pregnancy: (Annals of Oncology 21: 425-433, 2010)
38 patients: taking taxane Tx in 2nd & 3rd trimester.
27 patients were PABC patient.
Result:
- No spontaneous abortion/intrauterine death reported.
- 2 case exposed to paclitaxel were prematurity (30 &
32 wks, respectively) and developed acute respiratory
distress.
- 1 case with pyloric stenosis (the mother took
multiagent chemotherapy).
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Caution: no long-term safety data.
How about other regimens?
Item
Descriptions
Recommend
Trastuzumab
 For the pregnant patient,
the drug can result in oligohydramnios.
 Do not use it for the
pregnant patients.
Lapatinib
 Indication are approved only for
advanced HER-2 positive breast cancer.
 Just 1 case for PABC patient, no adverse
reactions were found.
 Need more data to
support its use for
pregnant patients.
Methotraxate
 With abortifacient and teratogenic effect.
 Can accumulate in 3rd fluid space
(amniotic fluid).
 Do not use it for the
pregnant patients.
Tamoxifen
 For the pregnant patient, the drug taken
 Do not use it for the
during pregnancy can result in
pregnant patients.
miscarriage, congenital malformation and
fetal death.
UPTODATE: Gestitional breast cancer: Treatment. 2014.
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Summary : regimen for PABC:
 The 2nd and 3rd trimester is much safer period for taking
chemotherapy.
 FAC/AC regimen is the first choice for PABC currently
due to its more sufficient data.
 Taxane regimen may be the choice for PABC patients.
 Short-term toxicity data seem to be safe.
(Prematurity and neutropenia need more caution.)
 Lorm-term toxicity data are insufficient and need further
follow-up.
 Trathuzumab, lapatinib, MTX, tamixifen are not
recommeded for the pregnant patients.
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Supportive treatment for PABC:
The following items can be administrated for
pregnant patient?
Antiemetics.
G-CSF.
Steroid.
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Antiemetics for PABC:
Antiemetics:
Type
Pregnancy
risk factor[3]
Neurokinin 1 antagonist
B
5-HT3 antagonist
B
Metoclopramide
B
Steroid
C/D
Descriptions[1],[2]
Can be used in all stages of pregnancy.
 Preferred prednisolone/hydrocortisone.
 Can be used after the 1st trimester.
[1]. Int J Gynecol Cancer 2009; 19: S1-S12.
[2]. EUROPEAN JOURNAL OF CANCER 46(2020)3158-3168.
[3]. UPTODATE: Drug information.
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Antiemetics for PABC:
G-CSFPregnancy risk factor: B[3]
For pregnant patient
 Can be used in all stages of pregnancy[1],[2].
 Ex[3].
 Filgrastim: IV/SC 5mg/kg/day
until the ANC ≥ 1000 /mm3
For the neonate
 Can be used in the neonate with neutropenia.[1],[2]
 Ex[3].
 Filgrastim: IV/SC 5-10 mg/kg/day for 3-5 days.
[1]. Int J Gynecol Cancer 2009; 19: S1-S12.
[2]. EUROPEAN JOURNAL OF CANCER 46(2020)3158-3168.
[3]. UPTODATE: Drug information.
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Steroid for PABC:
Steroid
Preferred or not
for pregnant
patient
Hydrocortisone
Preferred
Prednisolone
Preferred
Methylprednisolone
Preferred
Dexamethasone
Not preferred
Betamethasone
Not preferred
Descriptions[1],[2]
They were extensively metabolized in the
placenta and little crosses into the fetal
compartment.
 Animal study: repeated antenatal
exposure to dexa/betamethasone resulted
in animal model in decreased body and
brain weight.
 Although the difference was not
statistically significant, the higher rate of
cerebral palsy among children who had
been exposed to repeat doses of
corticosteroids(Betamethasone).
[1]. Int J Gynecol Cancer 2009; 19: S1-S12.
[2]. EUROPEAN JOURNAL OF CANCER 46(2020)3158-3168.
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Back to the patient (9/17):
Breast cancer: T1N1M0, ER(-), PR(-), HER2(+).
The patient performed MRM on 9/17, and the
gestational age is 12 wks).
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Back to the patient (9/17):
Timing consideration:
-We can perform the further chemotherapy after 2 wks
and should be stopped at GA 35 wks.
For the patient: 2014/10/1~ 2015/2/25 is the pregnant
period can be performed chemotherapy.
The FAC/AC may be suitable chemotherapy for the
patient.
Although the patient is HER-2 positive, Trastuzumab
can not be taken during pregnacy.
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Back to the patient (9/17):
Because the high emetic risk for FAC regimen,
the combinaiton of N1K antagonist, 5-HT3
antagonist and steroid should be taken.
Hydrocortisone, methylprednisolone, prednisolone
are preferred steroid.
G-CSF can be taken during the pregnancy.
If the neonate is neutropenia after birth, G-CSF can
be taken to prevent infection for the baby.
No breast feeding during chemotherapy.
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