Evolution of Angiogenic Factors in Pregnant Patients with Breast Cancer Treated with Chemotherapy

Abstract

Simple Summary Anthracyclines and taxanes are being used as a standard treatment for breast cancer diagnosed during pregnancy. These chemotherapy regimens allow the continuation of pregnancy without delaying cancer treatment with relatively good maternal and neonatal outcomes. However, their effects on placental function and fetal development are not completely understood. Maternal serum angiogenic factors are a surrogate of placental function and are abnormal weeks before placental complications such as preeclampsia or intrauterine growth restriction development. In our cohort, pregnant women with breast cancer treated with chemotherapy during pregnancy show an antiangiogenic state with significantly higher levels of soluble fms-like tyrosine kinase (sFlt-1), sFlt-1/PGF ratio, and soluble endoglin (sEng) at the end of the third trimester. Angiogenic factors could be useful in the clinical obstetric management of these patients, although more studies are guaranteed. High prevalence of placental-derived complications, such as preeclampsia and intrauterine growth restriction, has been reported in women with breast cancer (BC) treated with chemotherapy during pregnancy (PBC-CHT). Aim: To ascertain whether PBC-CHT is associated with an imbalance of angiogenic factors, surrogate markers for placental insufficiency, that could explain perinatal outcomes. Methods: Prospective study between 2012 and 2016 in a single institution. Soluble fms-like tyrosine kinase (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng) in maternal blood were assessed throughout pregnancy in 12 women with BC and 215 controls. Results: Cancer patients were treated with doxorubicin-based regimes and with taxanes. Ten PBC-CHT (83%) developed obstetrical complications. At the end of the third trimester, significantly higher levels of sFlt-1; sFlt-1/PGF ratio, and sEng levels were observed in BC women as compared to controls. Moreover; there was a significant correlation between plasma levels of sFlt-1 and the number of chemotherapy cycles administered. Besides, more chemotherapy cycles correlated with lower birthweight and head circumference at birth. Conclusions: Women with BC treated during pregnancy showed an antiangiogenic state compatible with placental insufficiency. Angiogenic factors could be useful in the clinical obstetric management of these patients; although further studies will be required to guide clinical decision-making.