Annals of Oncology Advance Access originally published online on September 2, 2008
Annals of Oncology 2008 19(10):1814-1815; doi:10.1093/annonc/mdn553
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letters to the editor |
Chemotherapy for breast cancer during pregnancy: is epirubicin safe?
The co-occurrence of cancer and pregnancy is becoming more frequent, given the trend for women to postpone childbearing [1]. As a consequence, the collection of more information about the effects of anticancer agents during pregnancy is useful to improve the existing guidelines.The most frequent solid tumour observed in pregnant women is breast cancer [1]. Among the drugs potentially active in these patients, taxanes and vinorelbine display a favourable safety profile, whereas trastuzumab is associated with severe foetal toxicity [1]. We and others have previously reported the feasibility of anthracyclines during the second and third trimesters of pregnancy [2, 3]. Recent international recommendations stated that anthracycline-based chemotherapy could be given to pregnant breast cancer patients during this period, with minimal risk to the developing foetus [3]. Although anthracyclines are a milestone of chemotherapy for breast cancer patients during pregnancy, only one prospective study was carried out in this setting [3] assessing the safety of a doxorubicin-based combination chemotherapy (FAC regimen). Hence, little is known about the safety of epirubicin, another anthracycline active in breast cancer, widely used in Europe.
We aimed to collect data on the safety of epirubicin in pregnant patients and therefore carried out a systematic review of the English literature in order to evaluate its maternal and embryo–foetal toxicity. Data for this review were identified by search of PubMed, Embase and Web of Knowledge, together with references from relevant articles, using the search terms ‘epirubicin AND pregnancy’ and ‘anthracyclines AND pregnancy’. Only papers published in English from 1967 to 1 July 2008 were included. Redundant publications (describing the same cohort of patients) were identified and only the most recent data were analysed.
A total of 13 publications [4–16] were identified, including three papers describing the same cohort of patients [4, 15, 16]. There were 48 cases of breast cancer, one case of non-Hodgkin’s lymphoma and one case of acute leukaemia.
The 50 cases are summarised in Table 1. Two of three administrations during the first trimester resulted in spontaneous abortions. Regarding the 47 administrations during the second and third trimesters, three serious events occurred: one intrauterine death at 30 weeks, one stillbirth and one neonatal death at day 8. All cases followed the administration of multiagent chemotherapy including cyclophosphamide (FEC, EC and FEC regimens, respectively), and the cause of death was not investigated [13, 14]. Maternal toxicity and neonatal status (Apgar scores and neonatal CBC) were scarcely reported.
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Basically, the use of epirubicin during the first trimester was associated with a dismal prognosis, whereas its use during the second and third trimesters resulted in 3of 47 (6%) unfavourable outcomes. This ratio was similar to that observed after administration of doxorubicin during the same period of pregnancy in a larger cohort of patients [2]. However, such results should be interpreted cautiously, given the methodological bias associated with the collection of data. Indeed, we hypothesise that unfavourable outcomes are well documented in the medical literature, whereas favourable outcomes are infrequently reported.
Moreover, preclinical data support the clinical experience suggesting that epirubicin and doxorubicin display similar toxicity profiles during pregnancy and share common pharmacological properties leading to a limited transplacental transfer. Hence, the transplacental passage of doxorubicin in placental perfusion studies was evaluated to 2.96% ± 0.75% [17], whereas a limited transplacental transfer of epirubicin was demonstrated as well, being evaluated to 3.66% ± 1.07% [18]. Both doxorubicin and epirubicin are substrates for the P-glycoprotein (Pgp/MDR1, ABCB1), which is highly expressed on the maternal compartment of the placenta [1]. The P-glycoprotein displays a major role in the protection of the foetus against a broad range of xenobiotics and might reduce the transplacental transfer of doxorubicin and epirubicin, making their clinical use possible during the second and third trimesters of pregnancy.
In conclusion, the decision of administrating chemotherapy during pregnancy should take into account the potential toxicity of anticancer agents for the mother and the foetus. This review of the literature evidenced a similar toxicity profile of epirubicin and doxorubicin during the second and third trimesters of pregnancy supported by pharmacological evidence. Further reports of anthracyclines administration during pregnancy are warranted in order to confirm their safety and to better handle these drugs in the obstetrical setting.
1 Department of Medical Oncology, Paris Descartes University, Paris
2 Department of Clinical Pharmacology, Teaching Hospital Cochin, Clinical Research Unit, Paris Public Assistance Hospital, Paris Descartes University, Faculty of Medicine, Paris
3 Department of Obstetrics, CALG Group: French group of ‘Cancers Associés à La Grossesse’, Paris
4 Department of Gynecology and Obstetrics, Teaching Hospital Saint-Antoine, Paris
5 Department of Gynecology and Obstetrics, Teaching Hospital Tenon, Paris
6 Department of Gynecology and Obstetrics, Teaching Hospital Cochin, Paris Public Assistance Hospital, Paris Descartes University, Faculty of Medicine, Paris, France
* (E-mail: olivier.mir{at}cch.aphp.fr)
References
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15. Azim HA Jr, Peccatori FA. Treatment of metastatic breast cancer during pregnancy: we need to talk! Breast (2008) Published on April 30, 2008. doi: 10.1016/j.breast.2008.02.005.
16. Azim HA Jr, Peccatori FA, Scarfone G, et al. Anthracyclines for gestational breast cancer: course and outcome of pregnancy. Ann Oncol (2008) 19:1511–1512.
17. Grohard P, Akbaraly JP, Saux MC, et al. Transplacental passage of doxorubicin. J Gynecol Obstet Biol Reprod (1989) 18:595–600.[Medline]
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  O. Mir, P. Berveiller, F. Goffinet, J.-M. Treluyer, R. Serreau, F. Goldwasser, and R. Rouzier Taxanes for breast cancer during pregnancy: a systematic review Ann. Onc., November 3, 2009; (2009) mdp517v1. [Full Text] [PDF]
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