Secondary leukemia after epirubicin-based adjuvant chemotherapy in operable breast cancer patients: 16 years experience of the French Adjuvant Study Group.
BACKGROUND
The purpose of this study was to evaluate incidence and risk factors of secondary leukemia after adjuvant epirubicin-based chemotherapy in breast cancer patients.


METHODS
Among eight French Adjuvant Study Group trials, 3653 patients were assessable: 2603 received epirubicin; 682 received hormonotherapy; and 368 had no systemic treatment. Chemotherapy was FEC regimen in 85% of cases (fluorouracil 500 mg/m2, epirubicin 50, 75 or 100 mg/m2, cyclophosphamide 500 mg/m2, three or six cycles). Epirubicin cumulative dose was <300 mg/m2 in 1045 patients; 300-600 mg/m2 in 1187; and > or =600 mg/m2 in 286, followed by radiotherapy in 96% of cases. The median follow-up was 104 months.


RESULTS
Eight cases of leukemia occurred in epirubicin-exposed patients and one in non-exposed patients. After 9 years, the risk of developing a leukemia was 0.34% (95% confidence interval 0.11-0.57) in epirubicin-exposed patients. In patients receiving chemotherapy, leukemia subtypes were: AML2 (two), AML3 (one), AML4 (three) and ALL (two). None of the classically recognized risk factors was significantly correlated with the occurrence of a leukemia.


CONCLUSIONS
Irrespective of the dose, the incidence of secondary leukemia after adjuvant epirubicin-based chemotherapy was low. After a long follow-up, the benefit/risk ratio for early breast cancer patients remained in favor of epirubicin-based adjuvant chemotherapy: eight cases (0.31%) occurred, and in some of them, treatment causality could be debatable.
Campone
M
M
m-campone@nantes.fnclcc.fr
Roché
H
H
Kerbrat
P
P
Bonneterre
J
J
Romestaing
P
P
Fargeot
P
P
Namer
M
M
Monnier
A
A
Montcuquet
P
P
Goudier
M-J
MJ
Fumoleau
P
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000627:therapeutic use; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D007951:Leukemia, Myeloid / Q000139:chemically induced / Q000145:classification / Q000188:drug therapy*; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013237:Stereoisomerism; D015996:Survival Rate
D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil