Disease-free survival advantage of adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with node-negative, rapidly proliferating breast cancer: a randomized multicenter study.
OBJECTIVE
According to one of the most recent key scientific questions concerning the use of biomarkers in clinical trials, we investigated whether node-negative breast cancer patients, defined as high-risk cases on the basis of tumor cell proliferation, could benefit from cyclophosphamide, methotrexate, and fluorouracil (CMF) adjuvant therapy.


METHODS
Two hundred eighty-one patients with negative nodes and rapidly proliferating tumors, defined according to thymidine labeling index (TLI), were randomized to receive six cycles of CMF or no further treatment after surgery +/- radiotherapy.


RESULTS
The 5-year disease-free survival (DFS) was 83% for patients treated with CMF compared with 72% in the control group (P: =.028). Adjuvant treatment reduced both locoregional and distant metastases. When clinical outcome was analyzed in cell kinetic subgroups characterized according to tertile criteria, compared with patients in the control arm, 5-year DFS was significantly higher after adjuvant CMF in patients with TLI values in the second (78% v 88%, respectively; P: =.037) and third tertiles (58% v 78%, respectively; P: =.024).


CONCLUSIONS
The results from this randomized clinical study indicate that patients with node-negative, rapidly proliferating tumors significantly benefit from adjuvant CMF.
Amadori
D
D
Department of Oncology, Pierantoni Hospital, Forli, Italy. divonco@ausl.fo.it
Nanni
O
O
Marangolo
M
M
Pacini
P
P
Ravaioli
A
A
Rossi
A
A
Gambi
A
A
Catalano
G
G
Perroni
D
D
Scarpi
E
E
Giunchi
D C
DC
Tienghi
A
A
Becciolini
A
A
Volpi
A
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D002455:Cell Division / Q000502:physiology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010349:Patient Compliance; D011446:Prospective Studies; D012307:Risk Factors
D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate