Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23.
OBJECTIVE
Uncertainty about the relative worth of doxorubicin/cyclophosphamide (AC) and cyclophosphamide/methotrexate/fluorouracil (CMF), as well as doubt about the propriety of giving tamoxifen (TAM) with chemotherapy to patients with estrogen receptor-negative tumors and negative axillary nodes, prompted the National Surgical Adjuvant Breast and Bowel Project to initiate the B-23 study.


METHODS
Patients (n = 2,008) were randomly assigned to CMF plus placebo, CMF plus TAM, AC plus placebo, or AC plus TAM. Six cycles of CMF were given for 6 months; four cycles of AC were administered for 63 days. TAM was given daily for 5 years. Relapse-free survival (RFS), event-free survival (EFS), and survival (S) were determined by using life-table estimates. Tests for heterogeneity of outcome used log-rank statistics and Cox proportional hazards models to detect differences across all groups and according to chemotherapy and hormonal therapy status.


RESULTS
No significant difference in RFS, EFS, or S was observed among the four groups through 5 years (P =.96,.8, and.8, respectively), for those aged < or = 49 years (P =.97,.5, and.9, respectively), or for those aged > or = 50 years (P =.7,.6, and.6, respectively). A comparison between all CMF- and all AC-treated patients demonstrated no significant differences in RFS (87% at 5 years in both groups, P =.9), EFS (83% and 82%, P =.6), or S (89% and 90%, P =.4). There were no significant differences in RFS, EFS, or S between CMF and AC in patients aged < or = 49 or > or = 50 years. No significant difference in any outcome was observed when chemotherapy-treated patients who received placebo were compared with those given TAM. RFS in both groups was 87% (P =.6), 87% in patients aged < or = 49 (P =.9), and 88% and 87%, respectively (P =.4), in those aged > or = 50 years.


CONCLUSIONS
There was no significant difference in the outcome of patients who received AC or CMF. TAM with either regimen resulted in no significant advantage over that achieved from chemotherapy alone.
Fisher
B
B
National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA 15212-5234, USA. bernard.fisher@nsabp.org
Anderson
S
S
Tan-Chiu
E
E
Wolmark
N
N
Wickerham
D L
DL
Fisher
E R
ER
Dimitrov
N V
NV
Atkins
J N
JN
Abramson
N
N
Merajver
S
S
Romond
E H
EH
Kardinal
C G
CG
Shibata
H R
HR
Margolese
R G
RG
Farrar
W B
WB
D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002945:Cisplatin; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil; D006801:Humans; D008207:Lymphatic Metastasis; D008727:Methotrexate; D008875:Middle Aged; D010349:Patient Compliance; D010919:Placebos; D011960:Receptors, Estrogen / Q000378:metabolism*; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage*
D010919:Placebos; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate