Matteo Lambertini1, Samuel Martel2, Christine Campbell3, Sébastien Guillaume1, Florentine S Hilbers4, Uwe Schuehly5, Larissa Korde6, Hatem A Azim7, Serena Di Cosimo8, Richard C Tenglin9, Jens Huober10, José Baselga11, Alvaro Moreno-Aspitia12, Martine Piccart-Gebhart1, Richard D Gelber13,14,15, Evandro de Azambuja1, Michail Ignatiadis1. 1. Department of Medicine, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium. 2. Department of Hemato-Oncology, CISSS Montérégie-Centre/Hôpital Charles-Le Moyne, Université de Sherbrooke, Quebec, Canada. 3. Frontier Science, Kingussie, United Kingdom. 4. Breast International Group, Brussels, Belgium. 5. Novartis Pharma AG, Basel, Switzerland. 6. National Cancer Institute, Bethesda, Maryland. 7. Department of Medicine, Division of Hematology/Oncology, American University of Beirut, Beirut, Lebanon. 8. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 9. Rapid City Regional Hospital, Rapid City, South Dakota. 10. Breast Center, University of Ulm, Ulm, Germany. 11. Memorial Sloan Kettering Cancer Center, New York, New York. 12. Mayo Clinic, Jacksonville, Florida. 13. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 14. Harvard TH Chan School of Public Health, Boston, Massachusetts. 15. Frontier Science and Technology Research Foundation, Boston, Massachusetts.
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.
RCT Entities:
BACKGROUND: Limited data exist on the safety of using anti-humanepidermal 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.
Authors: Kathryn J Ruddy; Daniel J Schaid; Ann H Partridge; Nicholas B Larson; Anthony Batzler; Lothar Häberle; Ralf Dittrich; Peter Widschwendter; Visnja Fink; Emanuel Bauer; Judith Schwitulla; Matthias Rübner; Arif B Ekici; Viktoria Aivazova-Fuchs; Elizabeth A Stewart; Matthias W Beckmann; Elizabeth Ginsburg; Liewei Wang; Richard M Weinshilboum; Fergus J Couch; Wolfgang Janni; Brigitte Rack; Celine Vachon; Peter A Fasching Journal: Fertil Steril Date: 2019-07-29 Impact factor: 7.329
Authors: Ingeborg J H Vriens; Elena M Ter Welle-Butalid; Maaike de Boer; Christine E M de Die-Smulders; Josien G Derhaag; Sandra M E Geurts; Irene E G van Hellemond; Ernest J T Luiten; M Wouter Dercksen; Bea M D Lemaire; Els R M van Haaren; Birgit E P J Vriens; Agnes J van de Wouw; Anne-Marie M G H van Riel; Sandra L E Janssen-Engelen; Marlène H W van de Poel; Ester E M Schepers-van der Sterren; Ron J T van Golde; Vivianne C G Tjan-Heijnen Journal: Breast Cancer Res Treat Date: 2020-03-31 Impact factor: 4.872