Timing of CMF chemotherapy in combination with tamoxifen in postmenopausal women with breast cancer: role of endocrine responsiveness of the tumor.
BACKGROUND
Controversy persists about whether chemotherapy benefits all breast cancer patients.


METHODS
In the International Breast Cancer Study Group (IBCSG) trial VII, 1212 postmenopausal patients with node-positive disease were randomized to receive tamoxifen for 5 years or tamoxifen plus three concurrent courses of cyclophosphamide, methotrexate and 5-fluorouracil ('classical' CMF) chemotherapy, either early, delayed or both. In IBCSG trial IX, 1669 postmenopausal patients with node-negative disease were randomized to receive either tamoxifen alone or three courses of adjuvant classical CMF prior to tamoxifen. Results were assessed according to estrogen receptor (ER) content of the primary tumor.


RESULTS
For patients with node-positive, ER-positive disease, adding CMF either early, delayed or both reduced the risk of relapse by 21% (P=0.06), 26% (P=0.02) and 25% (P=0.02), respectively, compared with tamoxifen alone. There was no difference in disease-free survival when CMF was given prior to tamoxifen in patients with node-negative, ER-positive tumors.


CONCLUSIONS
CMF given concurrently (early, delayed or both) with tamoxifen was more effective than tamoxifen alone for patients with node-positive, endocrine-responsive breast cancer, supporting late administration of chemotherapy even after commencement of tamoxifen. In contrast, sequential CMF and tamoxifen for patients with node-negative, endocrine-responsive disease was ineffective.
Colleoni
M
M
European Institute of Oncology, Milan, Italy. marco.colleoni@ieo.it
Li
S
S
Gelber
R D
RD
Coates
A S
AS
Castiglione-Gertsch
M
M
Price
K N
KN
Lindtner
J
J
Rudenstam
C-M
CM
Crivellari
D
D
Collins
J
J
Pagani
O
O
Simoncini
E
E
Thürlimann
B
B
Murray
E
E
Forbes
J
J
Erzen
D
D
Holmberg
S
S
Veronesi
A
A
Goldhirsch
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D016001:Confidence Intervals; D003520:Cyclophosphamide / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D015412:Mastectomy, Segmental; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017698:Postmenopause; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D018570:Risk Assessment; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D013629:Tamoxifen; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate