Tamoxifen adjuvant treatment duration in early breast cancer: initial results of a randomized study comparing short-term treatment with long-term treatment. Fédération Nationale des Centres de Lutte Contre le Cancer Breast Group.
OBJECTIVE
In 1986, The Fédération Nationale desCentres de Lutte Contre le Cancer Breast Group initiated a multicenter randomized trial to assess the usefulness of long-term adjuvant tamoxifen treatment. Short-term adjuvant tamoxifen treatment was to be compared with life long adjuvant tamoxifen treatment.


METHODS
Patients who were disease-free after 2 to 3 years of adjuvant tamoxifen treatment were eligible for the trial. From September 1986 to May 1995, 3,793 patients were randomized from France, Belgium, and Argentina. A total of 1,882 patients stopped tamoxifen (short-term group), and 1,911 patients were to continue tamoxifen for life (long-term group) at the same dose as previously prescribed. The protocol was modified in February 1997, limiting tamoxifen treatment to 10 years after randomization, thus giving a comparison between a 2- to 3-year treatment and a 12- to 13-year treatment. To date, the median duration of tamoxifen treatment is 30 months in the short-term group, and 70 months in the long-term group.


RESULTS
Overall, longer tamoxifen treatment induced a 23% reduction in relapse rates, leading to a 7-year disease-free survival rate of 78%, compared with 72% in the shorter-treatment group. In contrast, overall survival did not differ between the two groups, with a 79% overall survival rate in both groups. This improvement in disease-free survival could be observed in node-positive patients (P: =.001); however, it was not found in node-negative patients. Prolonged tamoxifen treatment corresponded to a significant increase in disease-free survival in estrogen receptor-positive patients (P: =.03) as well as in estrogen receptor-negative patients (P: =.05). Furthermore, longer treatment reduced contralateral breast cancers and did not increase the number of endometrial cancers.


CONCLUSIONS
Although no survival advantage was noted, patients did benefit from longer tamoxifen treatment over 3 years and had significantly better disease-free survival compared with patients who stopped hormonal treatment. Long-term follow-up is needed to assess these results. Most patients in the long-term group are still receiving treatment. Comparison of results as time passes will enable conclusions to be made on the value of long-term treatment over 5 years compared with 2 to 3 years.
Delozier
T
T
Fédération Nationale des Centres de Lutte Contre le Cancer, Paris, France. t.delozier@baclesse.fr
Spielmann
M
M
Macé-Lesec'h
J
J
Janvier
M
M
Hill
C
C
Asselain
B
B
Julien
J P
JP
Weber
B
B
Mauriac
L
L
Petit
J C
JC
Kerbrat
P
P
Malhaire
J P
JP
Vennin
P
P
Leduc
B
B
Namer
M
M
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016889:Endometrial Neoplasms / Q000139:chemically induced; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D011960:Receptors, Estrogen / Q000502:physiology; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage*
D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen; D013629:Tamoxifen