The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up.
BACKGROUND
The role of adjuvant dose-intensive chemotherapy and its efficacy according to baseline features has not yet been established.


METHODS
Three hundred and forty-four patients were randomized to receive seven courses of standard-dose chemotherapy (SD-CT) or three cycles of dose-intensive epirubicin and cyclophosphamide (epirubicin 200 mg/m(2) plus cyclophosphamide 4 mg/m(2) with filgrastim and progenitor cell support). All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). This paper updates the results and explores patterns of recurrence according to predicting baseline features.


RESULTS
At 8.3-years median follow-up, patients assigned DI-EC had a significantly better DFS compared with those assigned SD-CT [8-year DFS percent 47% and 37%, respectively, hazard ratio (HR) 0.76; 95% confidence interval 0.58-1.00; P = 0.05]. Only patients with estrogen receptor (ER)-positive disease benefited from the DI-EC (HR 0.61; 95% confidence interval 0.39, 0.95; P = 0.03).


CONCLUSIONS
After prolonged follow-up, DI-EC significantly improved DFS, but the effect was observed only in patients with ER-positive disease, leading to the hypothesis that efficacy of DI-EC may relate to its endocrine effects. Further studies designed to confirm the importance of endocrine responsiveness in patients treated with dose-intensive chemotherapy are encouraged.
Colleoni
M
M
Department of Medicine, Research Unit in Medical Senology, European Institute of Oncology, Milan, Italy. marco.colleoni@ieo.it
Sun
Z
Z
Martinelli
G
G
Basser
R L
RL
Coates
A S
AS
Gelber
R D
RD
Green
M D
MD
Peccatori
F
F
Cinieri
S
S
Aebi
S
S
Viale
G
G
Price
K N
KN
Goldhirsch
A
A
D000328:Adult; D000368:Aged; D000568:Amenorrhea; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011994:Recombinant Proteins; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome
D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D013629:Tamoxifen; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D000069585:Filgrastim