Trastuzumab, lapatinib and bevacizumab during pregnancy

Abstract

5 ISSN 1758-1923 10.2217/BMT.12.51 © 2013 Future Medicine Ltd Breast Cancer Manage. (2013) 2(1), 5–7 Breast cancer is one of the most common types of cancer in women of reproductive age and, thus, also one of the most often encountered types of cancer diagnosed during pregnancy. The estimated incidence varies from one in 3000 to one in 10,000 deliveries annually, depending on the study population used. As women postpone childbearing to a later age, the chance of developing a malignancy during pregnancy rises, and increasing incidence has recently been reported in two populationbased cohort studies from Sweden and Australia [1,2]. Historically, breast cancer during pregnancy (BCP) was viewed as a particularly aggressive and incurable type of cancer. However, as research has evolved, and oncologic treatment is more commonly applied during pregnancy, prognosis of BCP has also improved and is now comparable with prognosis of the nonpregnant patient [3]. We have advocated that treatment during pregnancy should be according to the standard as much as possible [4]. Based on available cohort studies, surgery and also chemotherapy (from 12–14 weeks gestation) is possible during pregnancy without impairment of fetal safety [5]. It is unclear whether or not a higher incidence of HER2 overexpression occurs in BCP when compared with nonpregnant controls [3]. Targeted therapy (e.g., trastuzumab, lapatinib and bevacizumab) has not been thoroughly investigated during pregnancy and clinical experience is very limited. The majority of targeted agents inhibit normal growth factors or angiogenesis, which might be harmful for the growth and development of the fetus. Trastuzumab is an IgG monoclonal antibody used for treating breast cancer overexpressing the HER2 receptor (~20–30% of all breast cancers), and is a member of the human EGF receptor (EGFR) family. Its use in the adjuvant setting is associated with significant improvement of survival [6,7]. Transplacental transport of trastuzumab to the fetus is comparable with transport of other IgG antibodies. IgG antibodies require active transport across the placental barrier and most of the IgG in a fetus is of maternal origin. Fetal IgG levels are very low in the first trimester; transport increases with gestational age and typically exceeds maternal IgG concentrations at full-term pregnancy [8]. Transplacental transport of trastuzumab in a pregnant baboon model showed similar