Randomized cooperative study of perioperative chemotherapy in breast cancer.
OBJECTIVE
The aim of this multicentric randomized trial was to determine whether reducing the interval between surgery and chemotherapy improves the outcome of breast cancer patients.


METHODS
Between June 1985 and July 1992, 600 breast cancer patients, clinical stages T1-3A,N0-2,M0 were randomly assigned to a perioperative cycle (PC) of cyclophosphamide 600 mg/m2, epidoxorubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF). Node-negative (N-) patients did not receive any further treatment. Node positive (N+) patients received 11 cycles if previously given PC, or 12 cycles of CEF alternated with cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 (CMF). In addition, N+ patients received concomitant or sequential 5-year tamoxifen therapy.


RESULTS
At a median follow-up duration of 5.7 years, no significant difference in survival (88% v 84%, P = .3) between the two treatment arms was seen. However, a difference of borderline significance in relapse-free survival (RFS; 76% v 70%, P = .053) was evident. A significant survival advantage for the PC arm was detected only in the estrogen receptor-negative (ER-) patients (P = .003). RFS was significantly improved in N- patients, postmenopausal patients, and ER- patients. Multivariate analyses show that pathologic tumor size, nodal status, receptor status, and treatment (only in ER- patients) are significantly correlated with survival and RFS. PC toxicity did not influence wound healing.


CONCLUSIONS
This study provides preliminary evidence that PC positively affects relapse rate and survival in some subgroups, namely, ER- patients.
Sertoli
M R
MR
Institute of Oncology, Genova University, Italy.
Bruzzi
P
P
Pronzato
P
P
Queirolo
P
P
Amoroso
D
D
Del Mastro
L
L
Venturini
M
M
Vigani
A
A
Bertelli
G
G
Campora
E
E
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D015999:Multivariate Analysis; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage
D011960:Receptors, Estrogen; D013629:Tamoxifen; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate