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Table 1 All eligible studies and case reports of trastuzumab administration during pregnancy in breast cancer patients

From: Trastuzumab administration during pregnancy: an update

Author Treatment during pregnancy Pathological type, Grade Stage at Pregnancy Age at BC diagnosis Age at pregnancy GA at trastuzumab GA at delivery Delivery Fetal outcome AEs during pregnnacy Initial Staging PFS OS
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, 2735 g 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 h Cardiotoxicity (LVEF decline: 61 to 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 min 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 min 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 3145 g (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, 5 min 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 2735 g 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: 3485 (2940–4180), 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
[38]
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
[39]
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