Department of Medicine, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium.
Department of Hemato-Oncology, CISSS Montérégie-Centre/Hôpital Charles-Le Moyne, Université de Sherbrooke, Quebec, Canada.
Cancer. 2019 Jan 15;125(2):307-316. doi: 10.1002/cncr.31784. Epub 2018 Oct 18.
Limited data exist on the safety of using anti-human epidermal growth factor receptor 2 (HER2) targeted agents during pregnancy. To date, only retrospective studies have assessed the prognosis of patients with a pregnancy after prior early breast cancer, with no data in HER2-positive patients.
The Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial and the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) trial were randomized phase 3 trials for patients with HER2-positive early breast cancer. In both trials, pregnancy information was prospectively collected. Pregnancy outcomes were compared between patients unintentionally exposed to trastuzumab and/or lapatinib during gestation (the exposed group) and those who became pregnant after trastuzumab and/or lapatinib completion (the unexposed group). In the ALTTO trial, disease-free survival (DFS) was compared between pregnant patients and those aged 40 years or younger without a subsequent pregnancy via an extended Cox model with time-varying covariates to account for a guarantee-time bias.
Ninety-two patients (12 in the exposed group and 80 in the unexposed group) had a pregnancy: 7 in the NeoALTTO trial and 85 in the ALTTO trial. Seven patients (58.3%) in the exposed group and 10 patients (12.5%) in the unexposed group opted for an induced abortion; in the unexposed group, 10 patients (12.5%) had a spontaneous abortion. No pregnancy/delivery complications were reported for the remaining cases, who successfully completed their pregnancy, with the exception of 1 fetus with trisomy 21 (Down syndrome). No significant difference in DFS (adjusted hazard ratio, 1.12; 95% confidence interval, 0.52-2.42) was observed between young patients with a pregnancy (n = 85) and young patients without a pregnancy (n = 1307).
For patients with HER2-positive early breast cancer, having a pregnancy after treatment completion appears to be safe without compromising fetal outcome or maternal prognosis.
关于在怀孕期间使用抗人表皮生长因子受体 2（HER2）靶向药物的安全性，目前仅有有限的数据。迄今为止，只有回顾性研究评估了既往早期乳腺癌后妊娠患者的预后，而在 HER2 阳性患者中尚无数据。
Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization（NeoALTTO）试验和 Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization（ALTTO）试验均为 HER2 阳性早期乳腺癌患者的随机 III 期试验。在这两项试验中，均前瞻性地收集妊娠信息。比较了妊娠期间意外暴露于曲妥珠单抗和/或拉帕替尼的患者（暴露组）与曲妥珠单抗和/或拉帕替尼完成后妊娠的患者（未暴露组）的妊娠结局。在 ALTTO 试验中，通过包含时变协变量的扩展 Cox 模型比较妊娠患者与未妊娠且年龄在 40 岁以下的患者的无病生存（DFS），以校正保证时间偏倚。
92 例患者（暴露组 12 例，未暴露组 80 例）妊娠：NeoALTTO 试验 7 例，ALTTO 试验 85 例。暴露组中 7 例（58.3%）患者选择人工流产，未暴露组中 10 例（12.5%）患者自然流产。其余病例未报告妊娠/分娩并发症，除 1 例胎儿为 21 三体（唐氏综合征）外，均成功完成妊娠。与未妊娠的年轻患者（n=1307）相比，妊娠的年轻患者（n=85）DFS 无显著差异（调整后的危险比，1.12；95%置信区间，0.52-2.42）。
对于 HER2 阳性早期乳腺癌患者，治疗后妊娠似乎是安全的，不会影响胎儿结局或母体预后。
