Table 1.
Summary of the reported cases with exposure to tamoxifen during pregnancy
| Study [Ref.], year | Cases, n | Tamoxifen indication | Tamoxifen exposure | Complications of pregnancy | GA at delivery, weeks | Way of delivery | Fetal outcome | Weight at delivery, g | Long-term neonatal outcome | Confounders (other exposures during pregnancy) |
|---|---|---|---|---|---|---|---|---|---|---|
| Koizumi and Aono [34], 1986 | 2 | Hyperprolactinemia and infertility due to pituitary adenoma | 1st trimester | NR | Case 1: 41; Case 2: 37 | Vaginal | Healthy at birth; no malformations | Case 1: 3,240; Case 2: 2,600 | NR | Bromocriptine |
| Clark [46], 1993 | 85 | Prevention of breast cancer | Unknown | No fetal anomalies | No information about duration of tamoxifen exposure and pregnancy outcome | |||||
| Cullins et al. [30], 1994 | 1 | Adjuvant hormone therapy for node-negative breast cancer | 1st and 2nd trimesters | Preterm labor and chorioamnionitis | 26 | CS | Normal karyotype; Goldenhar syndrome | 896 | NR | X-ray (bone scan using 99mTc) and drugs (cocaine and marijuana) |
| DiPaola et al. [44], 1997 | 1 | Multiple chemotherapy regimens for metastatic melanoma | 2nd and 3rd trimesters | CS due to progression of the tumor in the mother | 30 | CS | Healthy at birth; no malformations | 1,520 | Normal milestones up to 15 months | Carmustine, dacarbazine, cisplatin |
| Tewari et al. [29], 1997 | 1 | Hormone therapy for metastatic breast cancer | 1st and 2nd trimesters | Induction of labor due to deteriorating condition of the patient | 29 | Vaginal | Normal karyotype; ambiguous genitalia | 1,360 | NR | NR |
| Isaacs et al. [32], 2001 | 1 | Primary endocrine therapy for meta-static breast cancer | During whole pregnancy | CS due to deteriorating condition of the patient | 31 | CS | Normal karyotype; healthy at birth | 1,940 | Normal up to 2 years of age | Radiation and radiotherapy |
| Öksüzoglu and Güler [35], 2002 | 1 | Adjuvant hormone therapy for node-negative breast cancer | 1st trimester | NR | NR | NR | Healthy at birth; no malformations | NR | Normal milestones at 27 months | None |
| Andreadis et al. [41], 2004 | 1 | Hormone therapy for metastatic breast cancer | During whole pregnancy | Preterm labor | 35 | CS | Healthy at birth; no malformations | 2,070 | Normal milestones at 12 months | Biphosphonate, chemotherapy (FEC) and radiotherapy exposure |
| Li et al. [33], 2007 | 1 | Multiple chemotherapy regimens for metastatic melanoma | 1st and 2nd trimesters | NO | 34 | CS | Healthy at birth; no malformations | 2,750 | NR | Multiple chemotherapy regimens (carmustine, dacarbazine, cisplatin) during 1st and 2nd trimesters |
| Berger and Clericuzio [31], 2008 | 1 | Adjuvant hormone therapy for breast cancer | 1st trimester | 3rd trimester gestational diabetes; preeclampsia | 32 | Vaginal | Normal karyotype; microretrognathia, cleft of the secondary palate, glossoptosis: Pierre Robin sequence + left acetabular and sacral dysplasia | 1,983 | Unknown | 3rd trimester gestational diabetes; preeclampsia; use of ramelteon |
| Beale et al. [42], 2009 | 1 | Adjuvant hormone therapy for breast cancer | 1st and 2nd trimesters | Oligohydramnios; preterm premature rupture of membranes at 31+2 weeks | 31+6 | CS | Twin A: no malformations; renal failure at 12 weeks of age Twin B: no malformations | Twin A: 1,590 Twin B: 1,705 | Twin A: death at 13 weeks of age after respiratory arrest Twin B: unknown | Methadone; trastuzumab during 1st and 2nd trimesters; cigarette smoking; nifedipine tocolysis; preterm delivery |
| Warraich and Smith [43], 2009 | 1 | Adjuvant hormone therapy for breast cancer | Until 28 weeks | Anhydramnios | 37 | CS | No malformations; severe pulmonary hypoplasia and atelectasis | 2,690 | Death a few days after birth | Herceptin and goserelin assumption; exposure to radioactive scans |
| Grandvuillemin et al. [45], 2009 | 1 | NR | Until 16 weeks | NR | Medical abortion during 2nd trimester for maternal reason | NR | Female fetus with an enlarged clitoris | NR | NR | NR |
| Koca et al. [36], 2010 | 1 | Adjuvant hormone therapy for breast cancer | 1st trimester | Polyhydramniosis | 39 | CS | Healthy at birth; no malformations | 3,150 | Healthy in her 66th month | Radiotherapy and chemotherapy (FEC) exposure |
| Koca et al. [37], 2013 | 3 | Case 1: adjuvant endocrine therapy for metastatic breast cancer Case 2: adjuvant hormone therapy for breast cancer + LHRH Case 3: adjuvant hormone therapy | 1st trimester | NR | NR | NR | Healthy at birth in cases 1 and 2 Case 3: voluntary medical abortion at 6 weeks | NR | Case 1: normal up to 2 years of age Case 2: NR | Case 1: chemotherapy (paclitaxel, carboplatin, doxorubicin) |
| Ishizuka and Satou [38], 2016 | 1 | Adjuvant hormone therapy for breast cancer | 1st and 2nd trimesters | NR | At term | CS | Healthy at birth; no malformations | 2,544 | Normal up to 5 years of age | Goserelin while pregnancy unknown |
| Jyoti et al. [39], 2016 | 1 | Adjuvant hormone therapy for breast cancer | 1st trimester | NO | 39 | CS | Healthy at birth; no malformations | Normal but not specified | NR | NR |
| Mohamed and Mirghani [40], 2017 | 1 | Adjuvant hormone therapy for node-negative breast cancer | 1st and 2nd trimesters | NO | At term | NR | Healthy at birth; no malformations | NR | NR | NR |
| AstraZeneca safety database | 37 | NR | 1st trimester | NR | NR | NR | 2 live births with congenital anomalies: 1 girl delivered at 29 weeks with XXX chromosomes and also a phallus-like clitoris and huge labia, and 1 with idiopathic chylothorax; 2 elective terminations with fetal defects; 6 spontaneous abortions; 6 live births without congenital anomalies; 4 elective terminations (no fetal defects or unknown); 17 unknown | NR | NR | NR |
| AstraZeneca safety database | 15 | After 1st trimester | 1 live birth with congenital anomaly: congenital hand malformation; 1 elective termination with fetal defects; 9 live births without congenital anomaly; 1 elective termination (no fetal defects or unknown); 3 unknown | |||||||
| AstraZeneca safety database | 10 | During whole pregnancy | 1 live birth with congenital anomaly: Goldenhar syndrome (Cullins' report); 8 live births without congenital anomalies; 1 elective termination (no fetal defects or unknown) | |||||||
| AstraZeneca safety database | 74 | Unknown | 6 live births with congenital anomaly: 1 with cleft palate, 1 with ear malformation, 1 with trisomy 21, 1 with a small degree of labial fusion, 1 with craniofacial defects, and 1 with slight clitoral hypertrophy; 1 stillbirth with fetal defects; 3 elective terminations with fetal defects; 1 stillbirth without fetal defects; 5 spontaneous abortions; 1 ectopic pregnancy; 11 live births without congenital anomaly; 10 elective terminations (no fetal defects or unknown); 36 unknown | |||||||
| Lambertini et al. [48], 2019 | 1 | Hormone therapy for HER2-positive early breast cancer | 1st trimester | NR | 40 | CS | Healthy at birth; no malformations | 3,145 | NR | Lapatinib + trastuzumab exposure |
| Lareb database | 2 | NR | 1st trimester | NR | Case 1: at term Case 2: induced abortion | NR | Case 1: no congenital anomalies Case 2: induced abortion | NR | NR | NR |
| INCIP database | 2 | NR | 1st trimester | NR | Case 1: spontaneous abortion at 10 weeks Case 2: at term | NR | Case 1: spontaneous abortion Case 2: no congenital anomalies | NR | NR | NR |
| Current clinical case 1 | 1 | Adjuvant hormone therapy for breast cancer | 1st trimester | NO | 40 | Vaginal | Healthy at birth; no malformations | NR | Normal up to 6 years of age | NR |
| Current clinical case 2 | 1 | Adjuvant hormone therapy for breast cancer | 1st trimester | NO | At term | CS | Healthy at birth; no malformations | 3,160 | Regular | NR |
| Current clinical case 3 | 1 | Adjuvant hormone therapy for breast cancer | 1st trimester | NO | 34 | CS | Healthy at birth; no malformations | 2,800 | Regular until the last follow-up visit | NR |
GA, gestational age; NR, not reported; CS, cesarean section; LHRH, luteinizing hormone-releasing hormone.