Senologie - Zeitschrift für Mammadiagnostik und -therapie 2019; 16(03): 210-218
DOI: 10.1055/a-0977-4198
Wissenschaftliche Arbeit
© Georg Thieme Verlag KG Stuttgart · New York

Trastuzumab in der Behandlung schwangerer Mammakarzinompatientinnen – ein Literaturüberblick

Trastuzumab in the treatment of pregnant breast cancer patients – an overview of the literature
Sophia S. Goller
Universitätsklinikum Jena, Klinik für Geburtsmedizin, Placenta-Labor, Jena
,
Udo R. Markert
Universitätsklinikum Jena, Klinik für Geburtsmedizin, Placenta-Labor, Jena
,
Karolin Fröhlich
Universitätsklinikum Jena, Klinik für Geburtsmedizin, Placenta-Labor, Jena
› Author Affiliations
Further Information

Publication History

Publication Date:
11 September 2019 (online)

Zusammenfassung

Das Mammakarzinom gehört zu den am häufigsten in der Schwangerschaft auftretenden Malignomen. Da Frauen zunehmend erst in fortgeschrittenem Alter gebären, ist anzunehmen, dass die Inzidenz schwangerschaftsassoziierter Mammakarzinome zukünftig weiter steigen wird. Aufgrund schwangerschaftsbedingter Veränderungen und zurückhaltender Diagnostik kommt es häufig dazu, dass diese Karzinome erst in fortgeschrittenen Stadien detektiert werden und somit meist einer systemischen adjuvanten Therapie bedürfen. Verfügbare Daten bezüglich des optimalen chemotherapeutischen Managements sind limitiert. Insbesondere zur Anwendung des Target-Agents Trastuzumab, das in der Therapie des HER2-überexprimierenden Mammakarzinoms der nicht schwangeren Frau einen entscheidenden Beitrag zur Verbesserung der Prognose leisten konnte, fehlen dezidierte Informationen bezüglich des Wirk- und Sicherheitsprofils in der Schwangerschaft sowie auch hinsichtlich etwaiger Langzeiteffekte auf das Kind. Innerhalb der derzeit verfügbaren Literatur konnten 38 Schwangerschaften unter Trastuzumab zur Therapie eines Mammakarzinoms analysiert werden. Es lassen sich daraus Informationen gewinnen und Rückschlüsse ziehen, die zukünftig die Therapieoptionen der schwangeren Mammakarzinompatientin individualisieren und entscheidend verbessern können.

Abstract

Breast cancer is one of the most common malignancies which appear during pregnancy. Since women are increasingly not giving birth until they are at a more advanced age, it can be assumed that the incidence of pregnancy-related breast cancers will continue to increase in the future. Because of pregnancy-induced changes and conservative diagnosis, these carcinomas are frequently not detected until they are at an advanced stage and thus generally require systemic adjuvant therapy. The available data on optimal chemotherapeutic management are limited. Particularly for the use of the target agent trastuzumab which could crucially contribute to improving the prognosis in the therapy of HER2-overexpressing breast cancer in non-pregnant women, there is a lack of definitive information regarding the profile of action and safety in pregnancy as well as with regard to any long-term effects on the child. Thirty-eight pregnancies on trastuzumab for the treatment of breast cancer were able to be analysed in the literature currently available. Information can be gained from this and conclusions can be drawn which can individualise and decisively improve therapeutic options in the future for the pregnant breast cancer patient.

 
  • Literatur

  • 1 Pirvulescu C, Mau C, Schultz H. et al. Breast Cancer during Pregnancy: An Interdisciplinary Approach in Our Institution. Breast Care (Basel) 2012; 7: 311-314
  • 2 Stensheim H, Moller B, van Dijk T. et al. Cause-specific survival for women diagnosed with cancer during pregnancy or lactation: a registry-based cohort study. J Clin Oncol 2009; 27: 45-51
  • 3 Vetter G, Zimmermann F, Bruder E. et al. Aggressive Breast Cancer during Pregnancy with a Rare Form of Metastasis in the Maternal Placenta. Geburtsh Frauenheilk 2014; 74: 579-582
  • 4 Amant F, Loibl S, Neven P. et al. Breast cancer in pregnancy. Lancet 2012; 379: 570-579
  • 5 Dow KH. Pregnancy and breast cancer. J Obstet Gynecol Neonatal Nurs 2000; 29: 634-640
  • 6 Pavlidis NA. Coexistence of pregnancy and malignancy. Oncologist 2002; 7: 279-287
  • 7 Barnes DM, Newman LA. Pregnancy-associated breast cancer: a literature review. Surg Clin North Am 2007; 87: 417-430, x
  • 8 Keinan-Boker L, Lerner-Geva L, Kaufman B. et al. Pregnancy-associated breast cancer. Isr Med Assoc J 2008; 10: 722-727
  • 9 Loibl S. New Therapeutic Options for Breast Cancer during Pregnancy. Breast Care (Basel) 2008; 3: 171-176
  • 10 Loibl S. Adjuvant therapy in patients with breast cancer during pregnancy. Cancer Treat Res 2009; 151: 317-328
  • 11 Asgeirsson KS. Pregnancy-associated breast cancer. Acta Obstet Gynecol Scand 2011; 90: 158-166
  • 12 Salani R, Billingsley CC, Crafton SM. Cancer and pregnancy: an overview for obstetricians and gynecologists. Am J Obstet Gynecol 2014; 211: 7-14
  • 13 Voulgaris E, Pentheroudakis G, Pavlidis N. Cancer and pregnancy: a comprehensive review. Surg Oncol 2011; 20: e175-e185
  • 14 Cardoso F, Loibl S, Pagani O. et al. The European Society of Breast Cancer Specialists recommendations for the management of young women with breast cancer. Eur J Cancer 2012; 48: 3355-3377
  • 15 Loibl S, Schmidt A, Gentilini O. et al. Breast Cancer Diagnosed During Pregnancy: Adapting Recent Advances in Breast Cancer Care for Pregnant Patients. JAMA Oncol 2015; 1: 1145-1153
  • 16 Van Calsteren K, Heyns L, De Smet F. et al. Cancer during pregnancy: an analysis of 215 patients emphasizing the obstetrical and the neonatal outcomes. J Clin Oncol 2010; 28: 683-689
  • 17 Rich TA, Woodson AH, Litton J. et al. Hereditary breast cancer syndromes and genetic testing. J Surg Oncol 2015; 111: 66-80
  • 18 Sheikh A, Hussain SA, Ghori Q. et al. The spectrum of genetic mutations in breast cancer. Asian Pac J Cancer Prev 2015; 16: 2177-2185
  • 19 Woo JC, Yu T, Hurd TC. Breast cancer in pregnancy: a literature review. Arch Surg 2003; 138: 91-98 ; discussion 99
  • 20 Madaras L, Kovacs KA, Szasz AM. et al. Clinicopathological features and prognosis of pregnancy associated breast cancer – a matched case control study. Pathol Oncol Res 2014; 20: 581-590
  • 21 Pavlidis N, Pentheroudakis G. The pregnant mother with breast cancer: diagnostic and therapeutic management. Cancer Treat Rev 2005; 31: 439-447
  • 22 Loibl S, Han SN, Amant F. Being Pregnant and Diagnosed with Breast Cancer. Breast Care (Basel) 2012; 7: 204-209
  • 23 Amant F, Deckers S, Van Calsteren K. et al. Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer 2010; 46: 3158-3168
  • 24 Zemlickis D, Lishner M, Degendorfer P. et al. Maternal and fetal outcome after breast cancer in pregnancy. Am J Obstet Gynecol 1992; 166: 781-787
  • 25 Froehlich K, Stensheim H, Markert UR. et al. Breast carcinoma in pregnancy with spheroid-like placental metastases-a case report. APMIS 2018; 126: 448-452
  • 26 Molckovsky A, Madarnas Y. Breast cancer in pregnancy: a literature review. Breast Cancer Res Treat 2008; 108: 333-338
  • 27 Puckridge PJ, Saunders CM, Ives AD. et al. Breast cancer and pregnancy: a diagnostic and management dilemma. ANZ J Surg 2003; 73: 500-503
  • 28 Aebi S, Loibl S. Breast cancer during pregnancy: medical therapy and prognosis. Recent Results Cancer Res 2008; 178: 45-55
  • 29 Halaska MJ, Pentheroudakis G, Strnad P. et al. Presentation, management and outcome of 32 patients with pregnancy-associated breast cancer: a matched controlled study. Breast J 2009; 15: 461-467
  • 30 Cardonick E, Dougherty R, Grana G. et al. Breast cancer during pregnancy: maternal and fetal outcomes. Cancer J 2010; 16: 76-82
  • 31 Nami B, Maadi H, Wang Z. Mechanisms Underlying the Action and Synergism of Trastuzumab and Pertuzumab in Targeting HER2-Positive Breast Cancer. Cancers (Basel) 2018; DOI: 10.3390/cancers10100342.
  • 32 Slamon DJ, Leyland-Jones B, Shak S. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783-792
  • 33 Paik S, Bryant J, Tan-Chiu E. et al. Real-world performance of HER2 testing-National Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst 2002; 94: 852-854
  • 34 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Mammakarzinoms, Version 4.1, 2018. AWMF Registernummer: 032-045OL. Online: http://www.leitlinienprogrammonkologie.de/leitlinien/mammakarzinom/ ; Stand: 28.05.2018
  • 35 Spector NL, Blackwell KL. Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 2009; 27: 5838-5847
  • 36 Fiszman GL, Jasnis MA. Molecular Mechanisms of Trastuzumab Resistance in HER2 Overexpressing Breast Cancer. Int J Breast Cancer 2011; 2011: 352182
  • 37 Nuti M, Bellati F, Visconti V. et al. Immune effects of trastuzumab. J Cancer 2011; 2: 317-323
  • 38 Duong MN, Cleret A, Matera EL. et al. Adipose cells promote resistance of breast cancer cells to trastuzumab-mediated antibody-dependent cellular cytotoxicity. Breast Cancer Res 2015; 17: 57
  • 39 Maadi H, Nami B, Tong J. et al. The effects of trastuzumab on HER2-mediated cell signaling in CHO cells expressing human HER2. BMC Cancer 2018; 18: 238
  • 40 Niikura N, Liu J, Hayashi N. et al. Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol 2012; 30: 593-599
  • 41 Franklin MC, Carey KD, Vajdos FF. et al. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell 2004; 5: 317-328
  • 42 Baselga J, Cortes J, Kim SB. et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012; 366: 109-119
  • 43 Gianni L, Pienkowski T, Im YH. et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13: 25-32
  • 44 Lambertini M, Peccatori FA, Azim jr HA. Targeted agents for cancer treatment during pregnancy. Cancer Treat Rev 2015; 41: 301-309
  • 45 Wong Y, Raghavendra AS, Hatzis C. et al. Long-Term Survival of De Novo Stage IV Human Epidermal Growth Receptor 2 (HER2) Positive Breast Cancers Treated with HER2-Targeted Therapy. Oncologist 2019; 24: 313-318 . doi:10.1634/theoncologist.2018-0213
  • 46 Wolff AC, Hammond ME, Hicks DG. et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 2013; 31: 3997-4013
  • 47 Niikura N, Tomotaki A, Miyata H. et al. Changes in tumor expression of HER2 and hormone receptors status after neoadjuvant chemotherapy in 21755 patients from the Japanese breast cancer registry. Ann Oncol 2016; 27: 480-487
  • 48 Azim jr HA, 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 2012; 133: 387-391
  • 49 Petrek JA, Dukoff R, Rogatko A. Prognosis of pregnancy-associated breast cancer. Cancer 1991; 67: 869-872
  • 50 Amant F, Vandenbroucke T, Verheecke M. et al. Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy. N Engl J Med 2015; 373: 1824-1834
  • 51 Shlensky V, Hallmeyer S, Juarez L. et al. Management of Breast Cancer during Pregnancy: Are We Compliant with Current Guidelines?. AJP Rep 2017; 7: e39-e43
  • 52 Shen Y, Fujii T, Ueno NT. et al. Comparative efficacy of adjuvant trastuzumab-containing chemotherapies for patients with early HER2-positive primary breast cancer: a network meta-analysis. Breast Cancer Res Treat 2018; DOI: 10.1007/s10549-018-4969-6.
  • 53 Niraula S, Gyawali B. Optimal duration of adjuvant trastuzumab in treatment of early breast cancer: a meta-analysis of randomized controlled trials. Breast Cancer Res Treat 2018; DOI: 10.1007/s10549-018-4967-8.
  • 54 Poulsen MS, Rytting E, Mose T. et al. Modeling placental transport: correlation of in vitro BeWo cell permeability and ex vivo human placental perfusion. Toxicol In Vitro 2009; 23: 1380-1386
  • 55 Pacifici GM, Nottoli R. Placental transfer of drugs administered to the mother. Clin Pharmacokinet 1995; 28: 235-269
  • 56 Audus KL. Controlling drug delivery across the placenta. Eur J Pharm Sci 1999; 8: 161-165
  • 57 Syme MR, Paxton JW, Keelan JA. Drug transfer and metabolism by the human placenta. Clin Pharmacokinet 2004; 43: 487-514
  • 58 Robinson NR, Atkinson DE, Jones CJ. et al. Permeability of the near-term rat placenta to hydrophilic solutes. Placenta 1988; 9: 361-372
  • 59 Sibley CP. Review article: mechanisms of ion transfer by the rat placenta: a model for the human placenta?. Placenta 1994; 15: 675-691
  • 60 St-Pierre MV, Ugele B, Gambling L. et al. Mechanisms of drug transfer across the human placenta-a workshop report. Placenta 2002; 23: S159-S164
  • 61 Loebstein R, Lalkin A, Koren G. Pharmacokinetic changes during pregnancy and their clinical relevance. Clin Pharmacokinet 1997; 33: 328-343
  • 62 Juchau MR. Bioactivation in chemical teratogenesis. Annu Rev Pharmacol Toxicol 1989; 29: 165-187
  • 63 van der Aa EM, Peereboom-Stegeman JH, Noordhoek J. et al. Mechanisms of drug transfer across the human placenta. Pharm World Sci 1998; 20: 139-148
  • 64 Wong WM. Drug update: trastuzumab: anti-HER2 antibody for treatment of metastatic breast cancer. Cancer Pract 1999; 7: 48-50
  • 65 Saji F, Samejima Y, Kamiura S. et al. Dynamics of immunoglobulins at the feto-maternal interface. Rev Reprod 1999; 4: 81-89
  • 66 Takizawa T, Anderson CL, Robinson JM. A novel Fc gamma R-defined, IgG-containing organelle in placental endothelium. J Immunol 2005; 175: 2331-2339
  • 67 Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol 2009; 86: 328-344
  • 68 Sekar R, Stone PR. Trastuzumab use for metastatic breast cancer in pregnancy. Obstet Gynecol 2007; 110: 507-510
  • 69 Chailler P, Briere N. Mitogenic effects of EGF/TGF alpha and immunolocalization of cognate receptors in human fetal kidneys. Biofactors 1998; 7: 323-335
  • 70 Press MF, Cordon-Cardo C, Slamon DJ. Expression of the HER‑2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene 1990; 5: 953-962
  • 71 Robinson AA, Watson WJ, Leslie KK. Targeted treatment using monoclonal antibodies and tyrosine-kinase inhibitors in pregnancy. Lancet Oncol 2007; 8: 738-743
  • 72 Coelingh Bennink HJ, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric 2008; 11 (Suppl. 01) 47-58
  • 73 Pant S, Landon MB, Blumenfeld M. et al. Treatment of breast cancer with trastuzumab during pregnancy. J Clin Oncol 2008; 26: 1567-1569
  • 74 Meattini I, Curigliano G, Terziani F. et al. SAFE trial: an ongoing randomized clinical study to assess the role of cardiotoxicity prevention in breast cancer patients treated with anthracyclines with or without trastuzumab. Med Oncol 2017; 34: 75
  • 75 Fanale MA, Uyei AR, Theriault RL. et al. Treatment of metastatic breast cancer with trastuzumab and vinorelbine during pregnancy. Clin Breast Cancer 2005; 6: 354-356
  • 76 Watson WJ. Herceptin (trastuzumab) therapy during pregnancy: association with reversible anhydramnios. Obstet Gynecol 2005; 105: 642-643
  • 77 Waterston AM, Graham J. Effect of adjuvant trastuzumab on pregnancy. J Clin Oncol 2006; 24: 321-322
  • 78 Bader AA, Schlembach D, Tamussino KF. et al. Anhydramnios associated with administration of trastuzumab and paclitaxel for metastatic breast cancer during pregnancy. Lancet Oncol 2007; 8: 79-81
  • 79 Shrim A, Garcia-Bournissen F, Maxwell C. et al. Favorable pregnancy outcome following Trastuzumab (Herceptin) use during pregnancy-Case report and updated literature review. Reprod Toxicol 2007; 23: 611-613
  • 80 Berveiller P, Mir O, Sauvanet E. et al. Ectopic pregnancy in a breast cancer patient receiving trastuzumab. Reprod Toxicol 2008; 25: 286-288
  • 81 Weber-Schoendorfer C, Schaefer C. Untitled. Reprod Toxicol 2008; 25: 390-391
  • 82 Witzel ID, Muller V, Harps E. et al. Trastuzumab in pregnancy associated with poor fetal outcome. Ann Oncol 2008; 19: 191-192
  • 83 Azim jr HA, Peccatori FA, Liptrott SJ. et al. Breast cancer and pregnancy: how safe is trastuzumab?. Nat Rev Clin Oncol 2009; 6: 367-370
  • 84 Beale JM, Tuohy J, McDowell SJ. Herceptin (trastuzumab) therapy in a twin pregnancy with associated oligohydramnios. Am J Obstet Gynecol 2009; 201: e13-e14
  • 85 Goodyer MJ, Ismail JR, OʼReilly SP. et al. Safety of trastuzumab (Herceptin) during pregnancy: two case reports. Cases J 2009; 2: 9329
  • 86 Warraich Q, Smith N. Herceptin therapy in pregnancy: continuation of pregnancy in the presence of anhydramnios. J Obstet Gynaecol 2009; 29: 147-148
  • 87 Roberts NJ, Auld BJ. Trastuzamab (Herceptin)-related cardiotoxicity in pregnancy. J R Soc Med 2010; 103: 157-159
  • 88 Gottschalk I, Berg C, Harbeck N. et al. Fetal Renal Insufficiency Following Trastuzumab Treatment for Breast Cancer in Pregnancy: Case Report und Review of the Current Literature. Breast Care (Basel) 2011; 6: 475-478
  • 89 Mandrawa CL, Stewart J, Fabinyi GC. et al. A case study of trastuzumab treatment for metastatic breast cancer in pregnancy: fetal risks and management of cerebral metastases. Aust N Z J Obstet Gynaecol 2011; 51: 372-376
  • 90 El-Safadi S, Wuesten O, Muenstedt K. Primary diagnosis of metastatic breast cancer in the third trimester of pregnancy: a case report and review of the literature. J Obstet Gynaecol Res 2012; 38: 589-592
  • 91 Gupta S, Jain P, McDunn S. Breast cancer with brain metastases in pregnancy. J Community Support Oncol 2014; 12: 378-380
  • 92 Rasenack R, Gaupp N, Rautenberg B. et al. Case Report on Treatment of Metastatic Breast Cancer with Trastuzumab during Pregnancy. Z Geburtshilfe Neonatol 2016; 220: 81-83
  • 93 Andrade JM, Brito LG, Moises EC. et al. Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up. Anticancer Drugs 2016; 27: 369-372