EC Gynaecology

An unexpected pregnancy during the treatment of a neoplastic pathology is an increasingly frequent situation, amplifying the complexity of therapeutic management. Due to the impact of pregnancy on the oncological prognosis, and the potential teratogenic effects of anti-cancer agents.

Many birth defects have been reported in oncological patients undergoing chemotherapy. In order to improve the management of pregnancy-associated cancers, additional studies on the safety of the administration of anticancer agents during pregnancy should be conducted.

With the intention of bringing additional data to the scientific community, especially in this field where human study is difficult, mostly because of ethical issues, we present to readers a case of alobar holoprosencephaly (HPE) occurring following treatment for HER2+ breast cancer.

Keywords: Holoprosencephaly; Malformation; HER2+ Breast Cancer; Pregnancy; Trastuzumab; Case Report

1. Gianni L., et al. “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 Oncology3 (2011): 236-244.
2. Pentheroudakis G., et al. “Cancer, fertility and pregnancy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up”. Annals of Oncology 5 (2010): v266-v273.
3. Azim HA Jr., et al. “Treatment of cancer during pregnancy with monoclonal antibodies: a real challenge”. Expert Review of Clinical Immunology 6 (2010): 821-826.
4. Abusief ME., et al. “The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer”. Cancer 116.4 (2010): 791-798.
5. Harvey B., et al. “Neuroembryology”. In book: Youmans Neurological Surgery (2011): 78-97.
6. Matsunaga E and K Shiota. “Holoprosencephaly in human embryos: epidemiologic studies of 150 cases”. Teratology3 (1977): 261-272.
7. Tortori-Donati P and A Rossi. “Pediatric Neuroradiology”. Springer Verlag, Berlin Heidelberg New York (2020).
8. Hagn JS and PD Barnes. “Neuroimaging advances in holoprosencephaly: refining the spectrum of the midline malformation”. American Journal of Medical Genetics Part C: Seminars in Medical Genetics 1 (2010): 120-132.
9. Grangé Gilles and Lorraine Maitrot-Mantelet. “Guide pratique de l’échographie obstétricale et gynécologique”. Volume 15 (2016).
10. Ray Baud CH., et al. “Neuroradiologie pédiatrique”. s.d.
11. Srivastava K., et al. “Molecular analysis of the Noggin (NOG) gene in holoprosencephaly patients”. Molecular Genetics and Metabolism 2 (2012): 241-243.
12. Lidio G., et al. “Holoprosencephaly-report of two cases”. International Journal of Pediatric Otorhinolaryngology 11 (2005): 1563-1568.
13. Kauvar EF and M Muenke. “Holoprosencephaly: recommendations for diagnosis and management”. Current Opinion in Pediatrics 6 (2010): 687-695.
14. Lo HF., et al. “Concepts in multifactorial etiology of developmental disorders: gene-gene and gene-environment interactions in holoprosencephaly”. Frontiers in Cell and Developmental Biology 9 (2021): 795194.
15. Miller EA., et al. “Risk factors for non-syndromic holoprosencephaly in the National Birth Defects Prevention Study”. American Journal of Medical Genetics Part C: Seminars in Medical Genetics 1 (2010): 62-72.
16. Feijen EAM., et. al. “Derivation of anthracycline and anthraquinone equivalence ratios to doxorubicin for late-onset cardiotoxicity”. JAMA Oncology6 (2019): 864-871.
17. Minotti G., et al. “Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity”. Pharmacological Reviews 2 (2004): 185-229.
18. Legha SS., et al. “Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion”. Annals of Internal Medicine2 (1982): 133-139.
19. Swain SM., et al. “Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials”. Cancer11 (2003): 2869-2879.
20. Balanehru S and Nagarajan B. “Intervention of adriamycin induced free radical damage”. Biochemistry International 4 (1992): 735-744.
21. Fogli S., et al. “The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage”. FASEB Journal 6 (2004): 664-675.
22. Mihm MJ and Bauer JA. “Peroxynitrite-induced inhibition and nitration of cardiac myofibrillar creatine kinase”. Biochemie10 (2002): 1013-1019.
23. Kristel Van Calsteren., et al. “Transplacental Transfer of Paclitaxel, Docetaxel, Carboplatin, and Trastuzumab in a Baboon Model”. International Journal of Gynecological Cancer9 (2010): 1456-1464.
24. Shepard T. “Human teratogenicity”. Advances in Pediatrics 33 (1986): 225-268.
25. Goldenberg M. “Trastuzumab, a recombinant DNA-derived humanized monoclonal antibody, a novel agent for the treatment of metastatic breast cancer”. Clinical Therapeutics 2 (1999): 309-318.
26. Van Calsteren KV., et al. “Transplacental transfer of paclitaxel, docetaxel, carboplatin, and trastuzumab in a baboon model”. International Journal of Gynecological Cancer 9 (2010): 1456-1464.
27. Azim D., et al. “Pregnancy occurring during or following adjuvant trastuzumab in patients enrolled in the Hera trial (BIG 01-01)”. Breast Cancer Research and Treatment 1 (2012): 387-391.
28. Lin-Yu., et al. “Use of trastuzumab in treating breast cancer during pregnancy: a systematic review and meta-analysis”. BMC Womens Health1 (2021): 169.
29. Gottschalk I., et al. “Fetal renal insufficiency following trastuzumab treatment for breast cancer in pregnancy: case report und review of the current literature”. Breast Care6 (2011): 475-478.