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 |