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Cancer in Pregnancy: Breastfeeding and anti-cancer chemotherapy

Introduction

Breastfeeding is usually not recommended during maternal therapy with anti-cancer chemotherapy. This is because not only dose dependent effects but also possible dose-independent effects of these drugs cannot be completely ruled out. However, studies are scarce, and it is unclear how much morbidity risk of the infant is attributable to these drugs in milk.

Cisplatin
Results of two case reports 1,2 are in sharp contrast; one showed undetectable platinum in milk (<0.1 g/ml); and the other detected 0.9 g/ml platinum. Clinical significance of orally ingested cisplatin at this concentration is unknown.

Corticosteroids
Corticosteroids are considered safe to use during breastfeeding. The amount excreted into milk appears to be small enough to justify this notion 3.

Cyclophosphamide
There are two case reports on infants breastfed by mothers receiving the drug. Case 1 received weekly injection of 800 mg cyclophosphamide and 2 mg vincristine, and daily oral ingestion of 30mg predonisolone 4; Case 2 received 6 mg/kg/day cyclophosphamide intravenously 5. Although effects from intrauterine exposures to these drugs cannot be completely ruled out, observed neutropenia was considered to result from cyclophosphamide in milk.

Doxorubicin
The amount of doxorubicin and its metabolite excreted into milk is small, and so the infant dose is estimated to be small 1. However, there is no report on either successful or adversely-affected breastfeeding by a woman on doxorubicin.

Methotrexate
Methotrexate concentration was reported to be 6 n mol/L (2.6 ng/ml) in milk of a woman receiving 22.5 mg/day of the drug 6. Although the amount seems extremely low, more safety data are needed. Low dose regimen for arthritis may be considered safe 7, as long as dose-independent effects can be ignored.

Vincristine
No report is available on vincristine concentrations in human milk. Although neutropenia was ascribed to cyclophosphamide in the above mentioned case 4, the mother was also receiving vincristine.

Antibiotics
Antibiotics are considered compatible with breastfeeding. Although tetracyclines may cause discoloration of teeth, the amount of the drug available to the infant through milk may be sufficiently small as a result of binding to calcium in milk 7. However, alternatives should be tried first.

Anticoagulants
Regular heparin is not excreted into milk because of its high molecular weight. Low-molecular weight heparin (molecular weight of about 5,000) may be excreted into milk. However, heparin is not absorbed via oral route and therefore never administered orally. Warfarin is considered compatible with breastfeeding, because of its poor excretion into milk, and lack of effects on the infants 8.

Analgesics
As long as therapeutic doses are used, analgesics such as non-steroidal anti-inflammatory drugs and acetaminophen are considered compatible with breastfeeding. Morphine is also considered safe to use during breastfeeding 9.

Antiemetics
Domperidone and metoclopramide are excreted into milk in a small amount. They are also lactogenic to the mother because of their enhancing effects on prolactin. No adverse effect on the infant has been reported.

Allopurinol
Although a metabolite may be detected in the infant's plasma after breastfeeding by a woman taking allopurinol for hyperuricemia 10, no adverse effect has been reported.

Azathiopurine (6-mercaputopurine)
There are two reports on breastfeeding and azathiopurine use in organ transplant patients.10,11 Milk of two women taking azathiopurine (25 mg and 75 mg daily) contained lower than 20 g/l of active metabolite, 6-mercaputopurine. 10 This level of exposure translates into about 0.1% of the dose standardized by weight. In both reports, breast-fed infants showed no sign of toxicity. Some experts recommend formula feeding because of inherent toxicity of the drug, 12 while some suggest breast-feeding under close monitoring. 13

References

  1. Egan PC, Costanza ME, Dodion P, Egorin MJ, Bachur NR. Doxorubicin and cisplatin excretion into human milk. Cancer Treat Rep 1985;69:1387-1389.
  2. De Vries EGE, Van Der Zee AGJ, Uges DRA, Sleijfer DTh. Excretion of platinum into breast milk. Lancet 1989;1:497.
  3. Greenberger PA, Odeh YK, Frederiksen MC, Atkinson AJ Jr. Pharmacokinetics of prednisolone transfer to breast milk Clin Pharmacol Ther 1993;53:324-328.
  4. Amato D, Niblett JS. Neutropenia from cyclophosphamide in breast milk. Med J Aust 1977;1:383-384.
  5. Durodola JI, Administration of cyclophosphamide during late pregnancy and early lactation: a case report. J Natl Med Assoc 1979;71:165-166.
  6. Johns DG, Rutherford LD, Keighton PC, Vogel CL. Secretion of methotrexate into human milk. Am J Obstet Gynecol 1972;112:978-980.
  7. Anderson PO. Drug use during breast-feeding. Clin Pharm 1991;10:594-624.
  8. McKenna R, Cole ER, Vasan U. Is warfarin contraindicated in the lactating mother? J Pediatr 1983;103:325-327. American Academy of Pediatrics, Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137-150.
  9. Kamilli I, Gresser U. Allopurinol and oxypurinol in human breast milk. Clin Invest 1993;71:161-164.
  10. Coulam CB, Moyer TP, Jiang NS, Zincke H. Breast-feeding after renal transplantation. Transplant Proc 1982;14:605-609.
  11. Grekas DM, Vasiliou SS, Lazarides AN. Immunosuppressive therapy and breast-feeding after renal transplantation. Nephron 1984;37:68.
  12. Bennett PN, Matheson I, Notarianni LJ, Rane A, Reinhardt D. Monographs on individual drugs. In: Bennett PN ed. Drugs and Human Lactation, 2nd ed. Amsterdam: Elsevier, 1996:269-270.
  13. Anderson PO. Drug use during breast-feeding. Clin Pharm 1991;10:594-624.
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