Adjuvant chemotherapy for pregnant breast cancer patients. Case report: 2014/10/13 張嘉顯 1 (PABC; pregnancy-associated breast cancer)

Adjuvant chemotherapy for pregnant breast cancer patients.

Case report:

2014/10/13 張嘉顯

1

(PABC; pregnancy-associated breast cancer).

Patient information: (2014/10/10 OPD)

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History of present illness:

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Found bloody nipple discharge on right breast.

And also found she

had pregnacy.

Early 2014/8

2014/8/25

visited Jen-Ai Hospital for help. Core biopsy revealed an

invasive ductal carcinoma.

2014/9/9

Visited KFSYCC. Examination revealed infiltration ductal carcinoma(NG3,ER0,PR0, HER +++)

2014/9/17

Modified radical mastectomy.

Set port-A. Pregnancy termination.

(pregnacy for12 wks)

KSFYSCC OPD follow-up. Arrange the further

treatment.

Patient information: (2014/10/10 OPD)

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Problem list Breast cancer.Gastric ulcer.

How to perform the further treatment for the pregnant breast cancer patient?

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If the patient were not performed pregnant termination…

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.

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EUROPEAN JOURNAL OF CANCER 46(2020)3158-3168.

UPTODATE: Gestitional breast cancer: Treatment. 2014.

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.

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Treatment principles for PABC: Treatments for PABC are generally the same as non-

PABC, 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:

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Decrease disease-free survival. Increase risk of metastasis. (↑5-10 %Delay chemotherapy for 3-6 months).

Systemic treatment for PABC: Timing of treatment about trimester

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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:

The 1st trimester: 0-13 wks. The 2nd trimester: 14-26 wks. The 3rd trimester: 27-40 wks.

Systemic treatment for PABC: Timing of treatment (head?) :

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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.


Systemic treatment for PABC: Timing of treatment (tail?):

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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).


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.

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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.):

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Subjects Regimens and timing Efficacy outcomes(Follow-up:38.5 months)

57 PABC patient withoutmetastasis.

During 2nd ,3rd trimester (14-35 wks). FAC regimen:(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.

Free of disease and alive:40 pts. Had recurrent breast cancer: 3 pts. Death: 13 pts (12 pts for mets, 1 pts for

PE.)

FAC/AC regimen for PABC: Safety outcome (Cancer 2006; 107:1219):

No stillbirth/miscarriage.

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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)

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).

Caution: no long-term safety data. 20

How about other regimens?

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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).


Tamoxifen For the pregnant patient, the drug taken during pregnancy can result in miscarriage, congenital malformation and fetal death.



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:

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Type Pregnancy risk factor[3]

Descriptions[1],[2]

Neurokinin 1 antagonist B Can be used in all stages of pregnancy.

5-HT3 antagonist B

Metoclopramide B

Steroid C/D 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.

Antiemetics for PABC: G-CSFPregnancy risk factor: B[3]

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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.

Steroid for PABC:

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[1]. Int J Gynecol Cancer 2009; 19: S1-S12.[2]. EUROPEAN JOURNAL OF CANCER 46(2020)3158-3168.

Steroid Preferred or not for pregnant

patient

Descriptions[1],[2]

Hydrocortisone Preferred They were extensively metabolized in the placenta and little crosses into the fetal compartment.Prednisolone Preferred

Methylprednisolone Preferred

Dexamethasone Not preferred 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).

Betamethasone Not preferred

Back to the patient (9/17):

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Breast cancer: T1N1M0, ER(-), PR(-), HER2(+).The patient performed MRM on 9/17, and the

gestational age is 12 wks).


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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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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.

Documents

Adjuvant chemotherapy for pregnant breast cancer patients. Case report: 2014/10/13 張嘉顯 1 (PABC; pregnancy-associated breast cancer)