Which chemotherapy agent is contraindicated during pregnancy for treating breast cancer?

Methotrexate is Contraindicated During Pregnancy for Treating Breast Cancer

Methotrexate is absolutely contraindicated during pregnancy for treating breast cancer due to its severe teratogenic effects that can cause fetal death or serious birth defects. 1

Contraindications and Teratogenic Effects

• Methotrexate is classified as FDA Pregnancy Category X, meaning it is strictly contraindicated during pregnancy as it can cause fetal death and teratogenic effects 1, 2
• The drug acts as a folate antagonist, which is the primary mechanism behind its teratogenic effects 2
• When administered to pregnant women, methotrexate has been associated with:
  • Congenital malformations 3
  • Habitual abortions 2
  • Growth retardation 3
  • Craniofacial and digital anomalies 3

Safe Alternatives During Pregnancy

• Anthracycline-based regimens (including doxorubicin) are the most studied chemotherapeutic agents during pregnancy and remain the first choice for breast cancer treatment during pregnancy 4
• Weekly paclitaxel is the preferred option when taxanes are indicated or when anthracyclines are contraindicated 4
• 5-Fluorouracil, while also carrying pregnancy risks, can be used as part of anthracycline-based regimens (e.g., FAC, FEC) starting in the second trimester 4

Comparing the Options in the Question

• Methotrexate: Strictly contraindicated throughout pregnancy due to high risk of fetal malformations and pregnancy loss 1, 2, 5
• 5-Fluorouracil: Can be used as part of combination regimens starting in the second trimester, though it carries some risk 4, 6
• Doxorubicin: Can be safely administered during the second and third trimesters as part of anthracycline-based regimens 4, 7

Treatment Recommendations by Trimester

• First trimester: All chemotherapy should be avoided if possible due to high risk of teratogenicity 4
• Second and third trimesters: Anthracycline-based regimens (including doxorubicin) are considered safe 4
• Throughout pregnancy: Methotrexate and hormonal therapies like tamoxifen remain contraindicated at all times 4

Other Contraindicated Agents During Pregnancy

• Tamoxifen (hormonal therapy) is contraindicated throughout pregnancy due to risk of fetal malformations 4
• HER2-targeted therapies (trastuzumab, etc.) should be avoided during pregnancy due to risk of oligohydramnios 4
• PARP inhibitors, CDK4/6 inhibitors, and immune checkpoint inhibitors should also be avoided 4

Clinical Considerations

• For pregnant women with breast cancer, treatment decisions should be based on tumor biology, gestational age, and expected delivery date 4
• If treatment is necessary during pregnancy, it should ideally be delayed until after the first trimester 4
• A multidisciplinary team approach involving oncologists, maternal-fetal medicine specialists, and neonatologists is essential 7