Cancer management in pregnancy includes many chemotherapeutic agents generally considered to be at least potentially toxic to the embryo, fetus, or both. For the many novel polyclonal antibody therapies designated as antineoplastics, there are few data concerning their safety. Some risks with these and with other antineoplastic agents are discussed in Chapter 63 (p. 1191). A few of the more common agents for which experience in pregnancy has accrued are considered next.
This alkylating agent inflicts a chemical insult on developing fetal tissues and leads to cell death and heritable DNA alterations in surviving cells. Pregnancy loss rates are increased, and reported malformations include skeletal abnormalities, limb defects, cleft palate, and eye abnormalities (Enns, 1999; Kirshon, 1988). Surviving infants may have growth abnormalities and developmental delays. Environmental exposure among health-care workers is associated with a higher risk for spontaneous abortion (Chap. 18, p. 348).
This folic-acid antagonist is a potent terarogen. It is used for cancer chemotherapy, immunosuppression of autoimmune diseases and psoriasis, nonsurgical treatment of ecropic pregnancy, and medical abortion. It is similar in action to aminopterin, which is no longer used clinically, and can cause defects known collectively as the fetal methotrexate-aminopterin syndrome. This includes craniosynosrosis with a "clover-leaf' skull, wide nasal bridge, low-set ears, micrognathia, and limb abnormalities (Del Campo, 1999).
Teratology, Teratogens, and Fetotoxic Agents 243 he embryo is thought to be most vulnerable at 8 to 10 weeks postconception and at dosages of at least 10 mg/week. However, this is not universally accepted (Feldkamp, 1993).
he standard 50 mg/m2 dose given to treat ectopic pregnancy or to induce elective abortion exceeds this threshold dose. Some reports have suggested an association with cardiac anomalies, particularly conotruncal defects, in intrauterine pregnancies inadvertently treated with methotrexate for suspected ectopic pregnancy (Dawson, 2014; Hyoun, 2012). Thus, ongoing pregnancies after treatment with methotrexate-especially if used in conjunction with misoprostol-raise serious concerns for fetal malformations (N urmohamed, 2011).
This nonsteroidal selective estrogen-receptor modulator (SERM) is used as an adjuvant to treat breast cancer. No pattern of birth defects has been described in limited case reports and series (Braems, 2011). However, tamoxifen has been associated with malformations similar to those caused by diethylstilbestrol (DES) exposure in rodents, including vaginal adenosis. Consequently, women who become pregnant on therapy or within 2 months of its discontinuation should be apprised of the potentialilong-term risks of a DES-like syndrome.
his is a recombinant monoclonal antibody directed to the human epidermal growth factor receptor 2 (HER2) protein. Used to treat breast cancers that express HER2 protein, this drug has not been associated with fetal malformations. However, cases of oligohydramnios sequence resulting in pulmonary hypoplasia, renal failure, skeletal abnormalities, and neonatal deaths have been reported (Genentech, 2017). Surveillance for these complications is recommended for exposed pregnancies and for those treated at any time in the 7 months prior to conception. A trastuzumab pregnancy exposure registry and a pregnancy pharmacovigilance program have been established to monitor pregnancy outcomes. hese warnings also apply to those treated with ado-trastuzumab emtansine.