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Pregnancies during and after trastuzumab and/or lapatinib in patients with human epidermal growth factor receptor 2-positive early breast cancer: Analysis from the NeoALTTO (BIG 1-06) and ALTTO (BIG 2-06) trials

Matteo Lambertini, Samuel Martel, Christine Campbell, Sébastien Guillaume, Florentine S Hilbers, Uwe Schuehly, Larissa Korde, Hatem A Azim, Serena Di Cosimo, Richard C Tenglin, Jens Huober, José Baselga, Alvaro Moreno-Aspitia, Martine Piccart-Gebhart, Richard D Gelber, Evandro De Azambuja & Michail Ignatiadis

abstract

BACKGROUND
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.

METHODS
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.

RESULTS
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).

CONCLUSIONS
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.
   
citation Lambertini M, Martel S, Campbell C, Guillaume S, Hilbers F S, Schuehly U, Korde L, Azim H A, Di Cosimo S, Tenglin R C, Huober J, Baselga J, Moreno-Aspitia A, Piccart-Gebhart M, Gelber R D, de Azambuja E, Ignatiadis M. Pregnancies during and after trastuzumab and/or lapatinib in patients with human epidermal growth factor receptor 2-positive early breast cancer: Analysis from the NeoALTTO (BIG 1-06) and ALTTO (BIG 2-06) trials. Cancer 2018; 125:307-316.
   
type journal paper/review (English)
date of publishing 18-10-2018
journal title Cancer (125/2)
ISSN electronic 1097-0142
pages 307-316
PubMed 30335191
DOI 10.1002/cncr.31784