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Pregnancy occurring during or following adjuvant trastuzumab in patients enrolled in the HERA trial (BIG 01-01)

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Abstract

Only few case reports describe the pregnancy course and outcome of breast cancer patients, who were under treatment with trastuzumab at the time of conception or who have completed trastuzumab therapy before becoming pregnant. The HERA trial is a large phase III randomized clinical trial in which patients with early HER2-positive breast cancer were randomized to receive 1 or 2 years of trastuzumab or observation following completion of primary chemotherapy. To examine the effect of trastuzumab on pregnancy outcome, we report all pregnancy events that occurred until March 2010 in patients enrolled in the study. For the sake of this analysis, patients were assigned to three groups: (1) pregnancy occurring during and up to 3 months after trastuzumab exposure (group 1); (2) pregnancy occurring >3 months of last trastuzumab dose (group 2); and (3) pregnancy occurring in patients without prior exposure to trastuzumab (group 3). Sixteen, 45 and 9 pregnancies took place in groups 1, 2, and 3, respectively. 25 and 16% of patients in groups 1 and 2 experienced spontaneous abortion, the former being higher than figures reported in the general population. However, short-term fetal outcome appeared normal across the three groups. Only 2 congenital anomalies were reported, one in group 2 and one in group 3. No congenital anomalies were reported in those exposed to trastuzumab in utero. This is the first report from a large randomized trial assessing the effect of trastuzumab on pregnancy course and outcome. Based on our results, trastuzumab does not appear to affect fetal outcome in patients who manage to complete their pregnancy. We are currently initiating a collaboration to collect similar data from the other large adjuvant trastuzumab trials to confirm these findings.

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References

  1. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. New Engl J Med 353(16):1659–1672

    Article  PubMed  CAS  Google Scholar 

  2. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. New Engl J Med 353(16):1673–1684

    Article  PubMed  CAS  Google Scholar 

  3. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J (2011) Adjuvant trastuzumab in HER2-positive breast cancer. New Engl J Med 365(14):1273–1283

    Article  PubMed  CAS  Google Scholar 

  4. Abusief ME, Missmer SA, Ginsburg ES, Weeks JC, Partridge AH (2010) The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer. Cancer 116(4):791–798

    Article  PubMed  CAS  Google Scholar 

  5. Matthews TJ, Hamilton BE (2009) Delayed childbearing: more women are having their first child later in life. NCHS Data Brief 21:1–8

    PubMed  Google Scholar 

  6. Pant S, Landon MB, Blumenfeld M, Farrar W, Shapiro CL (2008) Treatment of breast cancer with trastuzumab during pregnancy. J Clin Oncol 26(9):1567–1569

    Article  PubMed  Google Scholar 

  7. Beale JM, Tuohy J, McDowell SJ (2009) Herceptin (trastuzumab) therapy in a twin pregnancy with associated oligohydramnios. Am J Obstet Gynecol 201(1):e13–e14

    Article  PubMed  Google Scholar 

  8. Bader AA, Schlembach D, Tamussino KF, Pristauz G, Petru E (2007) Anhydramnios associated with administration of trastuzumab and paclitaxel for metastatic breast cancer during pregnancy. Lancet Oncol 8(1):79–81

    Article  PubMed  Google Scholar 

  9. Witzel ID, Muller V, Harps E, Janicke F, Dewit M (2008) Trastuzumab in pregnancy associated with poor fetal outcome. Ann Oncol 19(1):191–192

    Article  PubMed  CAS  Google Scholar 

  10. Azim HA Jr, Peccatori FA, Liptrott SJ, Catania C, Goldhirsch A (2009) Breast cancer and pregnancy: how safe is trastuzumab? Nat Rev 6(6):367–370

    CAS  Google Scholar 

  11. Azim HA Jr, Azim H, Peccatori FA (2010) Treatment of cancer during pregnancy with monoclonal antibodies: a real challenge. Expert Rev Clin Immunol 6(6):821–826

    Article  PubMed  Google Scholar 

  12. Amant F, Deckers S, Van Calsteren K, Loibl S, Halaska M, Brepoels L, Beijnen J, Cardoso F, Gentilini O, Lagae L, Mir O, Neven P, Ottevanger N, Pans S, Peccatori F, Rouzier R, Senn HJ, Struikmans H, Christiaens MR, Cameron D, Du Bois A (2010) Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer 46(18):3158–3168

    Article  PubMed  Google Scholar 

  13. Azim HA Jr, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, Peccatori FA (2011) Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer 47(1):74–83

    Article  PubMed  Google Scholar 

  14. Pagani O, Partridge A, Korde L, Badve S, Bartlett J, Albain K, Gelber R, Goldhirsch A (2011) Pregnancy after breast cancer: if you wish, ma’am. Breast Cancer Res Treat 129(2):309–317

    Article  PubMed  Google Scholar 

  15. Dalberg K, Eriksson J, Holmberg L (2006) Birth outcome in women with previously treated breast cancer—a population-based cohort study from Sweden. PLoS Med 3(9):e336

    Article  PubMed  Google Scholar 

  16. Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sanchez Rovira P, Piccart-Gebhart MJ (2007) 2-Year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369(9555):29–36

    Article  PubMed  CAS  Google Scholar 

  17. Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, Untch M, Smith I, Baselga J, Jackisch C, Cameron D, Mano M, Pedrini JL, Veronesi A, Mendiola C, Pluzanska A, Semiglazov V, Vrdoljak E, Eckart MJ, Shen Z, Skiadopoulos G, Procter M, Pritchard KI, Piccart-Gebhart MJ, Bell R (2011) Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol 12(3):236–244

    Article  PubMed  CAS  Google Scholar 

  18. Mills JL, Simpson JL, Driscoll SG, Jovanovic-Peterson L, Van Allen M, Aarons JH, Metzger B, Bieber FR, Knopp RH, Holmes LB et al (1988) Incidence of spontaneous abortion among normal women and insulin-dependent diabetic women whose pregnancies were identified within 21 days of conception. New Engl J Med 319(25):1617–1623

    Article  PubMed  CAS  Google Scholar 

  19. Daniels S, Johnston M, Hiles L (2011) Herceptin (trastuzumab) and the incidence of spontaneous abortion. Drug Saf 34:987

    Google Scholar 

  20. Azim HA Jr, Peccatori FA, Pavlidis N (2010) Treatment of the pregnant mother with cancer: a systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part I: solid tumors. Cancer Treat Rev 36(2):101–109

    Article  PubMed  CAS  Google Scholar 

  21. Pentsuk N, van der Laan JW (2009) An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res 86(4):328–344

    Article  CAS  Google Scholar 

  22. Malek A (2003) Ex vivo human placenta models: transport of immunoglobulin G and its subclasses. Vaccine 21(24):3362–3364

    Article  PubMed  CAS  Google Scholar 

  23. de Azambuja E, Bedard PL, Suter T, Piccart-Gebhart M (2009) Cardiac toxicity with anti-HER-2 therapies: what have we learned so far? Target Oncol 4(2):77–88

    Article  PubMed  Google Scholar 

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Acknowledgment

Hatem A. Azim Jr. is supported by a research grant from the European Society for Medical Oncology. The authors would like to thank Carolyn Straehle for her editorial assistance during the preparation of the manuscript.

Conflict of interest

Martine Piccart-Gebhart: Consultancy, Honorarium (Roche); Evandro de Azambuja: Honorarium (Roche); Ekaterina Gresko: Employee (Roche); Mounir Arfi: Institution received funding from Roche; other authors: none declared.

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Authors and Affiliations

  1. Department of Medical Oncology, Institut Jules Bordet and l’Université Libre de Bruxelles (ULB), Boulevard de Waterloo 121, 1000, Brussels, Belgium

    Hatem A. Azim Jr., Otto Metzger-Filho, Evandro de Azambuja, Florine Focant & Martine Piccart-Gebhart

  2. Department of Medicine and Research, Klinikum Offenbach, Offenbach, Germany

    Sibylle Loibl

  3. F. Hoffmann-La Roche, Basel, Switzerland

    Ekaterina Gresko

  4. Frontier Science, Kincraig, Kingussie, Scotland, UK

    Mounir Arfi

Authors
  1. Hatem A. Azim Jr.
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  2. Otto Metzger-Filho
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  3. Evandro de Azambuja
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  4. Sibylle Loibl
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  5. Florine Focant
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  6. Ekaterina Gresko
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  7. Mounir Arfi
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  8. Martine Piccart-Gebhart
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Correspondence to Hatem A. Azim Jr..

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This study was conducted on behalf of the HERA study team.

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Azim, H.A., Metzger-Filho, O., de Azambuja, E. et al. Pregnancy occurring during or following adjuvant trastuzumab in patients enrolled in the HERA trial (BIG 01-01). Breast Cancer Res Treat 133, 387–391 (2012). https://doi.org/10.1007/s10549-012-1996-6

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  • DOI: https://doi.org/10.1007/s10549-012-1996-6

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