A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer.
BACKGROUND
Tamoxifen, taken for five years, is the standard adjuvant treatment for postmenopausal women with primary, estrogen-receptor-positive breast cancer. Despite this treatment, however, some patients have a relapse.


METHODS
We conducted a double-blind, randomized trial to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The primary end point was disease-free survival.


RESULTS
Of the 4742 patients enrolled, 2362 were randomly assigned to switch to exemestane, and 2380 to continue to receive tamoxifen. After a median follow-up of 30.6 months, 449 first events (local or metastatic recurrence, contralateral breast cancer, or death) were reported--183 in the exemestane group and 266 in the tamoxifen group. The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 (95 percent confidence interval, 0.56 to 0.82; P<0.001 by the log-rank test), representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent (95 percent confidence interval, 2.6 to 6.8) at three years after randomization. Overall survival was not significantly different in the two groups, with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group. Severe toxic effects of exemestane were rare. Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group (P=0.04).


CONCLUSIONS
Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment.
Coombes
R Charles
RC
Department of Cancer Medicine, Imperial College and Charing Cross Hospital, London, United Kingdom.
Hall
Emma
E
Gibson
Lorna J
LJ
Paridaens
Robert
R
Jassem
Jacek
J
Delozier
Thierry
T
Jones
Stephen E
SE
Alvarez
Isabel
I
Bertelli
Gianfilippo
G
Ortmann
Olaf
O
Coates
Alan S
AS
Bajetta
Emilio
E
Dodwell
David
D
Coleman
Robert E
RE
Fallowfield
Lesley J
LJ
Mickiewicz
Elizabeth
E
Andersen
Jorn
J
Lønning
Per E
PE
Cocconi
Giorgio
G
Stewart
Alan
A
Stuart
Nick
N
Snowdon
Claire F
CF
Carpentieri
Marina
M
Massimini
Giorgio
G
Bliss
Judith M
JM
van de Velde
Cornelius
C
D000284:Administration, Oral; D000368:Aged; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*
D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; C056516:exemestane