Adjuvant docetaxel for high-risk, node-negative breast cancer.
BACKGROUND
A regimen of docetaxel, doxorubicin, and cyclophosphamide (TAC) is superior to a regimen of fluorouracil, doxorubicin, and cyclophosphamide (FAC) when used as adjuvant therapy in women with node-positive breast cancer. The value of taxanes in the treatment of node-negative disease has not been determined.


METHODS
We randomly assigned 1060 women with axillary-node-negative breast cancer and at least one high-risk factor for recurrence (according to the 1998 St. Gallen criteria) to treatment with TAC or FAC every 3 weeks for six cycles after surgery. The primary end point was disease-free survival after at least 5 years of follow-up. Secondary end points included overall survival and toxicity.


RESULTS
At a median follow-up of 77 months, the proportion of patients alive and disease-free was higher among the 539 women in the TAC group (87.8%) than among the 521 women in the FAC group (81.8%), representing a 32% reduction in the risk of recurrence with TAC (hazard ratio, 0.68; 95% confidence interval [CI], 0.49 to 0.93; P=0.01 by the log-rank test). This benefit was consistent, regardless of hormone-receptor status, menopausal status, or number of high-risk factors. The difference in survival rates (TAC, 95.2%; FAC, 93.5%) was not significant (hazard ratio, 0.76; 95% CI, 0.45 to 1.26); however, the number of events was small (TAC, 26; FAC, 34). Rates of grade 3 or 4 adverse events were 28.2% with TAC and 17.0% with FAC (P<0.001). Toxicity associated with TAC was diminished when primary prophylaxis with granulocyte colony-stimulating factor was provided.


CONCLUSIONS
As compared with adjuvant FAC, adjuvant TAC improved the rate of disease-free survival among women with high-risk, node-negative breast cancer. (Funded by GEICAM and Sanofi-Aventis; ClinicalTrials.gov number, NCT00121992.).
Hospital General Universitario Gregorio Marañón, Madrid, Spain. mmartin@geicam.org
Miguel
M
Martín
Miguel A
MA
Seguí
Antonio
A
Antón
Amparo
A
Ruiz
Manuel
M
Ramos
Encarna
E
Adrover
Ignacio
I
Aranda
Alvaro
A
Rodríguez-Lescure
Regina
R
Grosse
Lourdes
L
Calvo
Agustí
A
Barnadas
Dolores
D
Isla
Purificación
P
Martinez del Prado
Manuel
M
Ruiz Borrego
Jerzy
J
Zaluski
Angels
A
Arcusa
Montserrat
M
Muñoz
José M
JM
López Vega
José R
JR
Mel
Blanca
B
Munarriz
Cristina
C
Llorca
Carlos
C
Jara
Emilio
E
Alba
Jesús
J
Florián
Junfang
J
Li
José A
JA
López García-Asenjo
Amparo
A
Sáez
María José
MJ
Rios
Sergio
S
Almenar
Gloria
G
Peiró
Ana
A
Lluch
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
D003520:Cyclophosphamide; D000077143:Docetaxel; D004317:Doxorubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D043823:Taxoids; C508053:ERBB2 protein, human