Yildirim et al. 2018 (9)
|
Trastuzumab, Pertuzumab
|
IDC, ER: -, PR: -, HER2: +
|
IV (liver, lung bone)
|
22
|
23
|
Prior to pregnancy − 20th GA week
|
Not delivered
|
-
|
Elective abortion at 27th GA week
|
Oligohydramnios/Anhydramnios, Right renal agenesis, IUGR, Right adrenal gland hyperplasia
|
IV
|
NR
|
NR
|
Rasenack et al. 2016 (10)
|
Trastuzumab
|
IDC, ER: +, PR: +, HER2: +
|
IV (retroperitoneal, supraclavicular, mediastinal, left hilar, upper abdominal LNs)
|
25
|
29
|
Prior to pregnancy – 24th GA week, 29th GA week
|
35th + 5 week
|
Cesarean section
|
Healthy at 3 years old, 2735g birth weight, Apgar 7/9/9
|
Oligohydramnios at 24th week, Recovered after trastuzumab interruption, Reappeared at 29th week after 8th trastuzumab dose
|
pT2N0M0
(08/2004)
|
> 72 months
|
> 72 months
|
Safadi et al. 2012 (11)
|
Trastuzumab, Vinorelbine
|
IDC scirrhous, ER: -, PR: -, HER2: +, Gr3
|
IV (bone)
|
32
|
32
|
30th GA week
|
33th + 5 week
|
Cesarean section
|
Healthy at 13 months, 1990 g birth weight, Apgar 8/9/9
|
Anhydramnios at 33 weeks
|
IV
|
> 13
|
> 13
|
Mandrawa et al 2011 (12)
|
Trastuzumab
|
IDC, ER: -, PR: -, HER2: +,
|
IV (brain)
|
25
|
28
|
Prior to pregnancy − 27th GA week
(9 doses in total, 3510 mg)
|
37 weeks
|
Vaginal delivery
|
Healthy at 28 months, 3060 g.
Birth weight, Transient Tachypnoea of the newborn
|
Oligohydramnios at 25th week, recovered after 2 weeks, recurred in 3d trimester
|
TxN0M0
|
2,75
|
> 52,25 months
|
Roberts et al. 2010 (13)
|
Trastuzumab
|
IDC, ER: -, PR: -, HER2: +, Gr3
|
T2N1M0
|
36
|
36
|
4th GA week to 21st GA week
|
37 weeks
|
Vaginal delivery
|
Healthy, 3200 g birth weight, Mild Transient Tachypnoea of the Newborn and CPAP for 24 hours
|
Cardiotoxicity (LVEF decline: 61–40%, CHF)
|
T2N1M0
|
> 9,25
|
> 9,25
|
Beale et al. 2009 (15)
|
Trastuzumab, Tamoxifen
|
IDC, ER: +, HER2: +, Gr3
|
TxNxM0
|
28
|
29
|
Prior to pregnancy − 22nd week, already received 9 doses of trastuzumab
|
31 + 6 weeks
|
Cesarean section
|
Twin A: 1590 g, Apgar 5/8/9, Intubated at 8 minutes for respiratory failure, Chronic renal failure and chronic lung disease, Death due to respiratory distress at 3 months
Twin B: Healthy at discharge, 1705 g, Apgar 8/10 Transient respiratory failure till day 3, Elevated creatinine
|
Severe oligohydramnios, recovered in Twin B but remained minimal in Twin A, Amnioinfusion in 30 + 2’ weeks,
Premature rupture of membranes (PROM)
|
TxNxM0
|
> 14
|
> 14
|
Smith et Warraich 2009 (16)
|
Trastuzumab, Tamoxifen, Goserelin
|
IDC, ER: +, HER2: +, Gr3
|
TxNxM0
|
35
|
35
|
7th GA week − 31st week
|
37 weeks
|
Cesarean section
|
Severe pulmonary hypoplasia and atelectasis, 2690 g birth weight, Death at 40 minutes after extubation
|
Persistent anhydramnios from 28th GA week till delivery
|
TxNxM0
|
> 14.25
|
> 14.25
|
Pant et al. 2008 (17)
|
Trastuzumab
|
IDC, Gr2/3, ER: -, PR: -, HER2: +
|
IV (lung)
|
30
|
32
|
Prior to pregnancy − 30th week, total dose 4200 mg
|
32 + 1 weeks
|
Vaginal delivery
|
Healthy at 5 years old, Normal Apgar values, 1810 g birth weight
|
Oligohydramnios from 25 to 32d week, premature rupture of membranes (PROM)
|
IIA (T1N1M0)- Radical mastectomy & Lymph node dissection (2 years before)
|
NR
|
> 129.5
|
Witzel et al. 2008 (18)
|
Trastuzumab
|
IDC, ER: +, PR: -, HER2: +, Gr2.
|
IV (lung, brain)
|
29
|
31
|
Prior to pregnancy − 27th GA weeks (9 cycles in total, total dose 56 mg/kg)
|
27 weeks
|
Cesarean section
|
Severe respiratory distress and strong capillary leak syndrome, necrotizing enterocolitis, 1015 g birth weight, Apgar 8/7/6, Death due to multiple organ failure at 5 months
|
Oligohydramnios and severe vaginal bleeding at 27th GA week,
|
T2NxM0
After neoadjuvant: pT0N0M0
|
> 1
|
> 37.25
|
Sekar and Stone 2007 (19)
|
Trastuzumab, Docetaxel
|
IDC, ER: -, PR: -, HER2: +, Gr2
|
IV (lung, brachial plexus)
|
25
|
28
|
23d GA week − 27th GA week (docetaxel 380 mg total dose, 1385 mg trastuzumab total dose)
|
36 + 2 weeks
|
Cesarean section
|
Healthy at delivery, 2230 g birth weight, Apgar 7/9
|
Anhydramnios and IUGR at 30th GA week
|
T2N2M0
(Radical mastectomy & Lymphadenectomy
|
> 22
|
> 100
|
Waterston and Graham (2006) (20)
|
Trastuzumab
|
IDC, Gr2, ER: -, PR: -, HER2: +
|
II (TxN1M0)
|
30
|
30
|
Prior to pregnancy – 3d GA week, total dose 523 mg during pregnancy
|
Term
|
Vaginal delivery
|
Healthy at delivery
|
No complications
|
II (TxN1M0)
|
> 9.25
|
> 9.25
|
Fanale et al. 2005 (21)
|
Trastuzumab, Vinorelbine
|
IDC, Gr3, ER: -, PR: -, HER2: +
|
IV (liver)
|
26
|
26
|
27th GA week − 34th GA week
|
34 + 5 weeks
|
Vaginal delivery
|
Healthy at 6 months old, 2270 g birth weight, Apgar score 9/9/10
|
Oligohydramnios
|
IIB (T2N1M0)
|
> 3
|
> 18.75
|
Watson et al. 2005 (22)
|
Trastuzumab
|
IDC, ER: -, PR: -, HER2: +
|
T2N3M0
|
28
|
28
|
Prior to pregnancy − 20th GA week
|
37,5 weeks
|
Vaginal delivery
|
Healthy at 6 months old, 2960 g birth weight, Apgar score 8/9
|
Anhydramnios
|
T2N3M0
|
> 16.5
|
> 16.5
|
Berwart et al. (2020)
(23)
|
Trastuzumab, Tamoxifen
|
Left: IDC, ER: +, PR: +, HER2: +
Right: IDC, ER: +, PR: +, HER2: -
|
T2N0M0
|
31
|
32
|
Prior to pregnancy − 16th GA week
Docetaxel: 20th GA week – 32d GA week
|
38 weeks
|
Cesarean section
|
Healthy at 3 years old, 3820 g birth weight
|
No complications
|
T2N1M0 (Left mastectomy + Lymphadenectomy)
|
12
|
> 48
|
Safi et al. (2019) (24)
|
Trastuzumab, Docetaxel, Cyclophosphamide
|
NR
|
NR
|
NR
|
NR
|
3d trimester
|
36 weeks
|
Vaginal Delivery
|
Mild Respiratory distress, 2380 g birth weight, Apgar score 10, Admitted to Special Care Nursery (SCN) and discharged on day 4
|
No complications
|
NR
|
NR
|
NR
|
Aktoz et al. 2020
(25)
|
Trastuzumab, Docetaxel
|
IDC, ER: -, PR: -, HER2: +
|
IV (liver)
|
37
|
37
|
22nd − 34th GA week (5 cycles)
|
35 + 3 weeks
|
Cesarean section
|
Healthy at delivery, 2850 g birth weight, Apgar 8/8/9
|
No complications
|
IV (liver)
|
> 3.5
|
> 3.5
|
Lambertini et al. 2019 (26)
|
Patient 3: Trastuzumab, Brain RT
Patient 4:
Trastuzumab, Lapatinib, Tamoxifen
(12 patients)
|
NR
|
NR
|
NR
|
Median:33 (30.0-36.5)
|
Patient 1,2: Prior to pregnancy – 3 months prior to pregnancy
Patient 3,4: 1st trimester
|
Patient 3: 34 weeeks
Median: 39 (36.5–39.5)
|
Patient 3: Cesarean section
3 Cesarean sections/ 1 vaginal delivery/ 1 missing
|
7/12 (58.3%) Elective abortion
No spontaneous abortions
Median birth weight 3145g (2880–3776)
Apgar 8–9/9–10
|
Patient1,2: No complications
Patient 3: IUGR
Patient 4: No complications
No oligohydramnios
No congenital malformations
|
NR
|
Patient 3: 1
Patient 4: -
|
Patient 3: 2
Patient 4: -
|
Shlensky et al. 2017
(27)
|
Trastuzumab, Doxorubicin, Cyclophosphamide, Paclitaxel
|
IDC, ER: -, PR: -, HER2: +
|
IV
|
NR
|
NR
|
15th GA week
|
33
|
Vaginal delivery
|
Healthy, Normal birth weight, 5min Apgar score > 7
|
Oligohydramnios at 33d GA week
|
IV
|
NR
|
NR
|
Andrade et al. 2016
(28)
|
Trastuzumab
|
IDC, ER: -, PR: -, HER2: +,
Gr2
|
III (T3N2M0)
|
31
|
32
|
Prior to pregnancy – 27th GA week and then 28th -31st GA week (11 cycles in total, 4400 mg total dose)
|
32 + 2 weeks
|
Cesarean section
|
Respiratory distress syndrome/Pulmonary infection, 1655 g birth weight, Apgar 4/10, Pulmonary hypertension/Persistence of the arterial canal
Low creatinine clearance (6.1 ml/min), Healthy at 7 years old
|
Oligohydramnios at 27th GA week, Anhydramnios at 31st GA week
|
III (T3N2M0)
|
32
|
> 96
|
Pianca et al. 2015 (29)
|
Trastuzumab
|
IDC, ER: -, PR: -, HER2: +,
Gr2
|
T2N0M0
|
30
|
31
|
2d trimester – 28th GA week (2 cycles in total)
|
37th week
|
Cesarean section
|
2735g birth weight, Apgar 4/8, O2 therapy at delivery, Healthy at 7 years old
|
Small abdominal circumference, Oligohydramnios at 29th GA week
|
T2N0M0
|
> 11.75
|
> 11.75
|
Gottschalk et al 2011 (30)
|
Trastuzumab, Docetaxel, Carboplatin
|
IDC, ER: +, PR: +, HER2: +, Gr2
+
DCIS
|
TxNxM0
|
38
|
38
|
14th GA week – 20th GA week weekly (7 cycles, 4 mg/kg)
|
33 + 2 weeks
|
Cesarean section
|
Dystrophic premature neonate at delivery, birth weight < 3rd percentile, Postpartum normal development and renal function
|
Anhydramnios, Fetal renal failure at 21st GA week, IUGR at 28th week
|
TxNxM0
|
> 5.9
|
> 5.9
|
Azim et al. 2012
(31)
|
Trastuzumab (16 patients)
|
TxNxM0/ Non metastatic
|
NR
|
NR
|
32.5 (26–40)
|
3 months prior to pregnancy – during pregnancy
|
40 (39–40) (n = 5)
|
NR
|
Healthy,
Mean birth weight: 3,485 (2,940–4,180), Mean Apgar score (10 min): 10 (9–10)
|
7 (44%) induced abortions
25% (4/16) spontaneous abortions
No oligohydramnios
No congenital abnormalities
|
TxNxM0
|
NR
|
NR
|
Goodyer et al. 2009 (32)
|
Trastuzumab
(2 patients)
|
Patient 1: ER: -, PR: -, HER2: +
Patient 2: ER: -, PR: -, HER2: +
|
Patient 1: IV (pleural effusion)
Patient 2: III
|
Patient 1: 30
Patient 2: 36
|
NR
|
Patient 1: Second trimester – 29th GA week
Patient 2: Prior to pregnancy – 6th GA week
|
Patient 1: 29 weeks
Patient 2:
39 weeks
|
Patient 1: Cesarean section
Patient 2:
Vaginal Delivery
|
Patient 1: Respiratory distress syndrome and conductive hearing loss at delivery, Mild hypertonia and hyperreflexia, 1220 g birth weight, Healthy at 3 years old with ongoing minimal tightness of Achilles tendon
Patient 2: Healthy at 2 years old, 2940 g birth weight, Events of gastroenteritis at 3, 8, 11 months
|
Patient 1: -
Patient 2: 1 of 2 viable fetal sacs
|
Patient 1: TxN + M0
Patient 2: III
|
Patient 1:
> 2
Patient2:
> 24
|
Patient 1:
> 36
Patient2:
> 24
|
Azim et al 2009 (33)
|
Trastuzumab
|
IDC, ER: -, PR: -, HER2: +, Gr3
|
II (T2N1M0)
|
29
|
30
|
Prior to pregnanacy − 1st GA week (1 cycle, 6 mg/kg)
|
39 weeks
|
Cesarean section
|
Healthy at 14 moths old, 3550 g birth weight,
|
No complications
|
II
(T2N1M0)
|
> 46
|
> 46
|
Schoendorfer et Schaefer 2008 (34)
|
Trastuzumab
|
NR
|
IV (lung)
|
NR
|
32
|
Prior to pregnancy – 23d GA week
|
27 + 4 weeks
|
Cesarean section
|
Multiple prematurity-related problems, Dysplastic/hypoplastic left kidney and renal congestion, Death at 4 months
|
Oligohydramnios at 23d GA week, Premature detachment of the placenta at 28th GA week
|
IV (lung)
|
> 8.25
|
> 8.25
|
Shrim et al 2007 (35)
|
Trastuzumab
|
IDC, ER: -, PR: -, HER2: +, Gr3
|
IV (lung, brain)
|
28
|
32
|
Prior to pregnancy – 24th GA week (3200 mg total dose)
|
37 weeks
|
Cesarean section
|
Healthy at 2 months old, 2600 g birth weight, Apgar 9/10, Transient tachypnea of the newborn, No maternal HF
|
Decreased maternal LVEF at 18th and 24th GA weeks
|
TxNxM0
|
> 22
|
> 100
|
Berveiller et al 2008 (36)
|
Trastuzumab
|
ER: -, PR: -, HER2: +
|
III (T2N2bM0)
|
43
|
45
|
Prior to pregnancy (14 months, 2 mg/kg)
|
-
|
-
|
Voluntary abortion
|
Cervico-isthmic pregnancy
|
III (T2N2bM0)
|
> 23
|
> 23
|
Bader et al 2007 (37)
|
Trastuzumab, Paclitaxel
|
ER: -, PR: +, HER2: +
|
IV (bone mets, spinal cord compression)
|
31
|
38
|
25th – 28th GA week (2 cycles, 14 mg/kg total dose)
|
32 + 1 weeks
|
Cesarean section
|
Bacterial sepsis, transient renal failure, RDS at delivery,
1460 g birth weight, Healthy at 3 months
|
Anhydramnios and IUGR at 32d GA week
|
I
|
> 7.75
|
> 16.75
|
Diakite et al. 2019
(41)
|
Trastuzumab
|
IDC, Gr2, ER: -, PR: +, HER2: +
|
T4N2aMx
|
32
|
33
|
Prior to pregnancy –first trimester
|
33d GA week
|
Cesarean section
|
Twin A: Respiratory distress, 1450 g birth weight, Death at 10 days
Twin B: 1550 g birth weight, Death at 40 days due to cardiorespiratory arrest
|
Fetal distress and oligohydramnios
|
T1NxMx
|
> 19.25
|
> 19.25
|
Gupta et al 2014
(42)
|
Trastuzumab, Paclitaxel
(Dexamethazone, RT)
|
IDC, Gr3, ER: -, PR: -, HER2: +
|
IV (brain)
|
24
|
24
|
Prior to pregnancy – 12th GA week & 3d trimester – 6 weeks postpartum
|
38 weeks
|
Cesarean section
|
Apgar 9/9, Healthy at 6 months old
Maternal LVEF mildly decreased, Disease progression in brain mets/Leptomeningeal spread
Death at 6 months postpartum
|
Brain metastases at 22nd GA week
No fetal complications
|
T4N3cMx
|
2.5
|
23
|