Adjuvant cyclophosphamide, methotrexate and fluorouracil in node-negative and estrogen receptor-negative breast cancer. Updated results.
BACKGROUND
Node-negative breast cancers are considered to comprise a subgroup which is amenable to cure with local-regional therapy alone. However, approximately 30% of affected patients present new disease manifestations within 10 years after surgery. To test the hypothesis that node-negative and estrogen receptor-negative breast cancer patients can benefit from adjuvant chemotherapy, a prospective randomized study was activated at the Istituto Nazionale Tumori of Milan in 1980.


METHODS
The study was conducted in 90 patients operated on for unilateral breast cancer who were then assigned to receive either 12 intravenous cycles of cyclophosphamide, methotrexate and fluorouracil (CMF) every three weeks, or no further treatment. Adjuvant chemotherapy was administered in the outpatient clinic of the Division of Medical Oncology. Patient characteristics were fairly well balanced between the two treatment groups except for primary tumor size: 58% of those with a primary tumor measuring > 2 cm in its largest diameter were randomized in the control group compared with 38% in the CMF regimen (P = 0.06).


RESULTS
At 12 years after surgery treatment outcome was significantly superior for patients given adjuvant CMF. The relapse-free survival rate was 71% (95% confidence limits (CL): 56-86) versus 43% (95% CL: 28-58), and total survival was 80% (95% CL: 68-92) versus 50% (95% CL: 34-66), respectively. The benefit from the administration of CMF was evident in all patient subsets and was not influenced by menopausal status.


CONCLUSIONS
The long-term results of this trial of adjuvant combination chemotherapy confirm our previous observations on the efficacy of adjuvant chemotherapy in node-negative breast cancer patients at high risk of early disease relapse.
Zambetti
M
M
Division of Medical Oncology, Istituto Nazionale Tumori, Milan, Italy.
Valagussa
P
P
Bonadonna
G
G
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D016001:Confidence Intervals; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007558:Italy; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000502:physiology; D015996:Survival Rate
D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D011960:Receptors, Estrogen; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate