SAN ANTONIOA long-term Dutch study has provided
additional evidence that the duration of tamoxifen (Nolvadex) therapy
influences the degree of benefit for reducing breast cancer
recurrence. However, the optimal duration of therapy remains an open
question, Dr. Jan Vermorken, an oncologist at University Hospital,
Antwerp, said at the San Antonio Breast Cancer Symposium.
Nine Years of Follow-up
After 9 years of follow-up, weve found that
recurrence-free and overall survival are significantly improved when
a patient receives tamoxifen vs no tamoxifen, Dr. Vermorken
said. Weve also found during 7.2 years of follow-up that
continuation of tamoxifen for 3 years leads to a better
recurrence-free interval than stopping at 1 year (see Table
1). However, he added, we are not sure whether 5 years is
better than 3 years.
Dr. Vermorken believes that when other trials are done in the
future, 3 years of tamoxifen therapy could be a standard for the
The study also showed that tamoxifen reduces the risk of
contralateral breast cancer (see Table 2).
Additionally, Dr. Vermorken reported that the benefits of tamoxifen
in this study were restricted to estrogen-receptor (ER)-positive patients.
The findings emerged from a randomized clinical evaluationfrom
the Comprehensive Cancer Center Amsterdam (CCCA) Cooperative Breast
Cancer Groupinvolving more than 1,600 postmenopausal patients
with stage T1-4, N0-2, M0 breast cancer.
A total of 1,242 patients were stratified by axillary node status
and, after initial curative therapy, randomized to receive tamoxifen
(30 mg/d) for 1 year or no tamoxifen (first randomization). If
patients receiving tamoxifen were relapse-free after 1 year, they
were re-randomized to stop treatment or to continue tamoxifen for
another 2 years (second randomization).
Because interim data analyses showed that tamoxifen significantly
improved progression-free survival in patients with positive nodes,
after 1989 all node-positive patients received tamoxifen from the
start and, like other patients in the tamoxifen arm, were randomized
after 1 year to stop the drug or continue therapy for 2 more years.
(These patients contributed to the second randomization.)
The first randomization occurred in a 2:1 ratio of tamoxifen to
placebo, and 828 patients received tamoxifen. The second
randomization involved a total of 991 patients. Median follow-up from
first randomization exceeds 9 years, and median follow-up from second
randomization has reached 7.2 years.
Patients receiving tamoxifen did better at all endpoints. From first
randomization, tamoxifen resulted in recurrence-free survival rates
of 75.5% at 5 years and 57.2% at 10 years, compared with 67.6% and
50.7%, respectively, in the control group. Overall survival was 82.2%
and 64.2% at 5 and 10 years with tamoxifen vs 78.6% and 56.6%,
respectively, in the control group.
Following second randomization, continuation of tamoxifen for a total
of 3 years was associated with a recurrence-free survival rate of
75.4% at 5 years and 58.5% at 10 years, compared with 72.4% and
52.7%, respectively, for patients who stopped tamoxifen therapy after
a year. The 5- and 10-year overall survival figures were 80.7% and
64.1%, respectively, for 3 years of tamoxifen therapy vs 77.7% and
61.8% in patients who received tamoxifen for 1 year.
The analysis showed higher than expected event rates in ER-positive
patients who did not receive tamoxifen, as well as in all ER-negative
patients. The event rate was lower than expected (158 vs 191.8) in
ER-positive patients who received tamoxifen.
Contralateral Breast Cancer
From first randomization, 84 (10.1%) tamoxifen patients developed
second primary cancers, and 28 of these (33%) were contralateral
breast cancers. That compared with 48 second primaries (11.6%) in
patients who received no tamoxifen, 23 (47.9%) of which were
contralateral breast cancers.
Following second randomization, 21 of 52 (40.4%) second primary
cancers were contralateral breast cancers in patients who stopped
tamoxifen after a year. That compared with 15 of 45 (33%) in patients
who continued therapy for 3 years.
The results demonstrate significant improvement in
recurrence-free and overall survival with tamoxifen vs control,
Dr. Vermorken said. The effect is clearest in ER-positive
patients. Though not statistically significant, a trend toward
improved recurrence-free and overall survival is associated with
longer use of tamoxifen, specifically 3 years vs 1 year. The optimal
duration of tamoxifen therapy remains to be determined.